SRX278557 GSM1143089_1 SRP022854 GSE47023 SRS421409 GSM1143089 MNase-Seq GENOMIC MNase The strains were grown in medium at 30°C overnight. The same number of young, old and histone H3/H4 overexpressing cells were collected and the cells were cross-linked with formaldehyde. The cells were washed twice in 1xPBS buffer and pelleted. Then cells were resuspended in the Zymolyase buffer (1M sorbitol, 50 mM Tris-HCl at pH 7.4, and 10 mM b- Mercaptoethanol) for cell wall digestion with zymolyase-100T. After zymolyase-100T treatment, spheroplasts were pelleted and then resuspended in NP buffer (1M sorbitol, 50 mM NaCl, 10 mM Tris-HCl at pH 7.4, 5 mM MgCl2, 1mM CaCl2 and 0.075% Nonidet P40, and 500 mM spermidine). Micrococcal nuclease (MNase) was added to a final concentration of 1 U MNase/sample. The digestion reactions were incubated at 37°C for 30 min, and were stopped by adding SDS to a final concentration of 1% and EDTA to a final concentration of 10 mM. 5 ml of proteinase K solution was added to each tube. To reverse the formaldehyde cross-links, samples were incubated at 65°C overnight. Samples were extracted with 1 volume phenol/chloroform-IAA and centrifuged at room temperature for 15 min. DNA was precipitated with 2-propanol and washed with 70% ethanol. The pellet was dried at room temperature. 10 ml sterile ddH2O was added to the pellet. Then the DNA was treated with 1 ml RNase A (1mg/ml) at 37°C for 30 min. To check the mononucleosomal DNA fragments and MNase digestion level, electrophoresis was carried out on a 2% agarose gel. Samples were further analyzed on a Bioanalyzer 2100 to determine quality prior to library preparation. The libraries were generated using a KAPA library preparation kit (KK8200, Illumina Series). A spike-in control which mimics the size of the mononucleosomal fragment was included during the library construction, and was added according to the number of cells used to isolate the mononucleosomal fragments. The spike-in control used here comprises a set of three DNA sequences that were each around 150 nucleotides in length, with GC contents that mimic the GC% of the S. cerevisiae genome but with no significant similarity to the yeast genome. DNA fragments were size-selected between 200-400 bp after ligation of 121 bp adapters (Next flexTM DNA Barcodes-6). Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143089 gds 301143089 GEO Accession GSM1143089 SRX278558 GSM1143090_1 SRP022854 GSE47023 SRS421410 GSM1143090 MNase-Seq GENOMIC MNase The strains were grown in medium at 30°C overnight. The same number of young, old and histone H3/H4 overexpressing cells were collected and the cells were cross-linked with formaldehyde. The cells were washed twice in 1xPBS buffer and pelleted. Then cells were resuspended in the Zymolyase buffer (1M sorbitol, 50 mM Tris-HCl at pH 7.4, and 10 mM b- Mercaptoethanol) for cell wall digestion with zymolyase-100T. After zymolyase-100T treatment, spheroplasts were pelleted and then resuspended in NP buffer (1M sorbitol, 50 mM NaCl, 10 mM Tris-HCl at pH 7.4, 5 mM MgCl2, 1mM CaCl2 and 0.075% Nonidet P40, and 500 mM spermidine). Micrococcal nuclease (MNase) was added to a final concentration of 1 U MNase/sample. The digestion reactions were incubated at 37°C for 30 min, and were stopped by adding SDS to a final concentration of 1% and EDTA to a final concentration of 10 mM. 5 ml of proteinase K solution was added to each tube. To reverse the formaldehyde cross-links, samples were incubated at 65°C overnight. Samples were extracted with 1 volume phenol/chloroform-IAA and centrifuged at room temperature for 15 min. DNA was precipitated with 2-propanol and washed with 70% ethanol. The pellet was dried at room temperature. 10 ml sterile ddH2O was added to the pellet. Then the DNA was treated with 1 ml RNase A (1mg/ml) at 37°C for 30 min. To check the mononucleosomal DNA fragments and MNase digestion level, electrophoresis was carried out on a 2% agarose gel. Samples were further analyzed on a Bioanalyzer 2100 to determine quality prior to library preparation. The libraries were generated using a KAPA library preparation kit (KK8200, Illumina Series). A spike-in control which mimics the size of the mononucleosomal fragment was included during the library construction, and was added according to the number of cells used to isolate the mononucleosomal fragments. The spike-in control used here comprises a set of three DNA sequences that were each around 150 nucleotides in length, with GC contents that mimic the GC% of the S. cerevisiae genome but with no significant similarity to the yeast genome. DNA fragments were size-selected between 200-400 bp after ligation of 121 bp adapters (Next flexTM DNA Barcodes-6). Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143090 gds 301143090 GEO Accession GSM1143090 SRX278559 GSM1143091_1 SRP022854 GSE47023 SRS421411 GSM1143091 MNase-Seq GENOMIC MNase The strains were grown in medium at 30°C overnight. The same number of young, old and histone H3/H4 overexpressing cells were collected and the cells were cross-linked with formaldehyde. The cells were washed twice in 1xPBS buffer and pelleted. Then cells were resuspended in the Zymolyase buffer (1M sorbitol, 50 mM Tris-HCl at pH 7.4, and 10 mM b- Mercaptoethanol) for cell wall digestion with zymolyase-100T. After zymolyase-100T treatment, spheroplasts were pelleted and then resuspended in NP buffer (1M sorbitol, 50 mM NaCl, 10 mM Tris-HCl at pH 7.4, 5 mM MgCl2, 1mM CaCl2 and 0.075% Nonidet P40, and 500 mM spermidine). Micrococcal nuclease (MNase) was added to a final concentration of 1 U MNase/sample. The digestion reactions were incubated at 37°C for 30 min, and were stopped by adding SDS to a final concentration of 1% and EDTA to a final concentration of 10 mM. 5 ml of proteinase K solution was added to each tube. To reverse the formaldehyde cross-links, samples were incubated at 65°C overnight. Samples were extracted with 1 volume phenol/chloroform-IAA and centrifuged at room temperature for 15 min. DNA was precipitated with 2-propanol and washed with 70% ethanol. The pellet was dried at room temperature. 10 ml sterile ddH2O was added to the pellet. Then the DNA was treated with 1 ml RNase A (1mg/ml) at 37°C for 30 min. To check the mononucleosomal DNA fragments and MNase digestion level, electrophoresis was carried out on a 2% agarose gel. Samples were further analyzed on a Bioanalyzer 2100 to determine quality prior to library preparation. The libraries were generated using a KAPA library preparation kit (KK8200, Illumina Series). A spike-in control which mimics the size of the mononucleosomal fragment was included during the library construction, and was added according to the number of cells used to isolate the mononucleosomal fragments. The spike-in control used here comprises a set of three DNA sequences that were each around 150 nucleotides in length, with GC contents that mimic the GC% of the S. cerevisiae genome but with no significant similarity to the yeast genome. DNA fragments were size-selected between 200-400 bp after ligation of 121 bp adapters (Next flexTM DNA Barcodes-6). Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143091 gds 301143091 GEO Accession GSM1143091 SRX278560 GSM1143092_1 SRP022854 GSE47023 SRS421412 GSM1143092 MNase-Seq GENOMIC MNase The strains were grown in medium at 30°C overnight. The same number of young, old and histone H3/H4 overexpressing cells were collected and the cells were cross-linked with formaldehyde. The cells were washed twice in 1xPBS buffer and pelleted. Then cells were resuspended in the Zymolyase buffer (1M sorbitol, 50 mM Tris-HCl at pH 7.4, and 10 mM b- Mercaptoethanol) for cell wall digestion with zymolyase-100T. After zymolyase-100T treatment, spheroplasts were pelleted and then resuspended in NP buffer (1M sorbitol, 50 mM NaCl, 10 mM Tris-HCl at pH 7.4, 5 mM MgCl2, 1mM CaCl2 and 0.075% Nonidet P40, and 500 mM spermidine). Micrococcal nuclease (MNase) was added to a final concentration of 1 U MNase/sample. The digestion reactions were incubated at 37°C for 30 min, and were stopped by adding SDS to a final concentration of 1% and EDTA to a final concentration of 10 mM. 5 ml of proteinase K solution was added to each tube. To reverse the formaldehyde cross-links, samples were incubated at 65°C overnight. Samples were extracted with 1 volume phenol/chloroform-IAA and centrifuged at room temperature for 15 min. DNA was precipitated with 2-propanol and washed with 70% ethanol. The pellet was dried at room temperature. 10 ml sterile ddH2O was added to the pellet. Then the DNA was treated with 1 ml RNase A (1mg/ml) at 37°C for 30 min. To check the mononucleosomal DNA fragments and MNase digestion level, electrophoresis was carried out on a 2% agarose gel. Samples were further analyzed on a Bioanalyzer 2100 to determine quality prior to library preparation. The libraries were generated using a KAPA library preparation kit (KK8200, Illumina Series). A spike-in control which mimics the size of the mononucleosomal fragment was included during the library construction, and was added according to the number of cells used to isolate the mononucleosomal fragments. The spike-in control used here comprises a set of three DNA sequences that were each around 150 nucleotides in length, with GC contents that mimic the GC% of the S. cerevisiae genome but with no significant similarity to the yeast genome. DNA fragments were size-selected between 200-400 bp after ligation of 121 bp adapters (Next flexTM DNA Barcodes-6). Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143092 gds 301143092 GEO Accession GSM1143092 SRX278561 GSM1143093_1 SRP022854 GSE47023 SRS421413 GSM1143093 MNase-Seq GENOMIC MNase The strains were grown in medium at 30°C overnight. The same number of young, old and histone H3/H4 overexpressing cells were collected and the cells were cross-linked with formaldehyde. The cells were washed twice in 1xPBS buffer and pelleted. Then cells were resuspended in the Zymolyase buffer (1M sorbitol, 50 mM Tris-HCl at pH 7.4, and 10 mM b- Mercaptoethanol) for cell wall digestion with zymolyase-100T. After zymolyase-100T treatment, spheroplasts were pelleted and then resuspended in NP buffer (1M sorbitol, 50 mM NaCl, 10 mM Tris-HCl at pH 7.4, 5 mM MgCl2, 1mM CaCl2 and 0.075% Nonidet P40, and 500 mM spermidine). Micrococcal nuclease (MNase) was added to a final concentration of 1 U MNase/sample. The digestion reactions were incubated at 37°C for 30 min, and were stopped by adding SDS to a final concentration of 1% and EDTA to a final concentration of 10 mM. 5 ml of proteinase K solution was added to each tube. To reverse the formaldehyde cross-links, samples were incubated at 65°C overnight. Samples were extracted with 1 volume phenol/chloroform-IAA and centrifuged at room temperature for 15 min. DNA was precipitated with 2-propanol and washed with 70% ethanol. The pellet was dried at room temperature. 10 ml sterile ddH2O was added to the pellet. Then the DNA was treated with 1 ml RNase A (1mg/ml) at 37°C for 30 min. To check the mononucleosomal DNA fragments and MNase digestion level, electrophoresis was carried out on a 2% agarose gel. Samples were further analyzed on a Bioanalyzer 2100 to determine quality prior to library preparation. The libraries were generated using a KAPA library preparation kit (KK8200, Illumina Series). A spike-in control which mimics the size of the mononucleosomal fragment was included during the library construction, and was added according to the number of cells used to isolate the mononucleosomal fragments. The spike-in control used here comprises a set of three DNA sequences that were each around 150 nucleotides in length, with GC contents that mimic the GC% of the S. cerevisiae genome but with no significant similarity to the yeast genome. DNA fragments were size-selected between 200-400 bp after ligation of 121 bp adapters (Next flexTM DNA Barcodes-6). Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143093 gds 301143093 GEO Accession GSM1143093 SRX278562 GSM1143094_1 SRP022854 GSE47023 SRS421414 GSM1143094 MNase-Seq GENOMIC MNase The strains were grown in medium at 30°C overnight. The same number of young, old and histone H3/H4 overexpressing cells were collected and the cells were cross-linked with formaldehyde. The cells were washed twice in 1xPBS buffer and pelleted. Then cells were resuspended in the Zymolyase buffer (1M sorbitol, 50 mM Tris-HCl at pH 7.4, and 10 mM b- Mercaptoethanol) for cell wall digestion with zymolyase-100T. After zymolyase-100T treatment, spheroplasts were pelleted and then resuspended in NP buffer (1M sorbitol, 50 mM NaCl, 10 mM Tris-HCl at pH 7.4, 5 mM MgCl2, 1mM CaCl2 and 0.075% Nonidet P40, and 500 mM spermidine). Micrococcal nuclease (MNase) was added to a final concentration of 1 U MNase/sample. The digestion reactions were incubated at 37°C for 30 min, and were stopped by adding SDS to a final concentration of 1% and EDTA to a final concentration of 10 mM. 5 ml of proteinase K solution was added to each tube. To reverse the formaldehyde cross-links, samples were incubated at 65°C overnight. Samples were extracted with 1 volume phenol/chloroform-IAA and centrifuged at room temperature for 15 min. DNA was precipitated with 2-propanol and washed with 70% ethanol. The pellet was dried at room temperature. 10 ml sterile ddH2O was added to the pellet. Then the DNA was treated with 1 ml RNase A (1mg/ml) at 37°C for 30 min. To check the mononucleosomal DNA fragments and MNase digestion level, electrophoresis was carried out on a 2% agarose gel. Samples were further analyzed on a Bioanalyzer 2100 to determine quality prior to library preparation. The libraries were generated using a KAPA library preparation kit (KK8200, Illumina Series). A spike-in control which mimics the size of the mononucleosomal fragment was included during the library construction, and was added according to the number of cells used to isolate the mononucleosomal fragments. The spike-in control used here comprises a set of three DNA sequences that were each around 150 nucleotides in length, with GC contents that mimic the GC% of the S. cerevisiae genome but with no significant similarity to the yeast genome. DNA fragments were size-selected between 200-400 bp after ligation of 121 bp adapters (Next flexTM DNA Barcodes-6). Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143094 gds 301143094 GEO Accession GSM1143094 SRX278563 GSM1143095_1 SRP022854 GSE47023 SRS421415 GSM1143095 MNase-Seq GENOMIC MNase The strains were grown in medium at 30°C overnight. The same number of young, old and histone H3/H4 overexpressing cells were collected and the cells were cross-linked with formaldehyde. The cells were washed twice in 1xPBS buffer and pelleted. Then cells were resuspended in the Zymolyase buffer (1M sorbitol, 50 mM Tris-HCl at pH 7.4, and 10 mM b- Mercaptoethanol) for cell wall digestion with zymolyase-100T. After zymolyase-100T treatment, spheroplasts were pelleted and then resuspended in NP buffer (1M sorbitol, 50 mM NaCl, 10 mM Tris-HCl at pH 7.4, 5 mM MgCl2, 1mM CaCl2 and 0.075% Nonidet P40, and 500 mM spermidine). Micrococcal nuclease (MNase) was added to a final concentration of 1 U MNase/sample. The digestion reactions were incubated at 37°C for 30 min, and were stopped by adding SDS to a final concentration of 1% and EDTA to a final concentration of 10 mM. 5 ml of proteinase K solution was added to each tube. To reverse the formaldehyde cross-links, samples were incubated at 65°C overnight. Samples were extracted with 1 volume phenol/chloroform-IAA and centrifuged at room temperature for 15 min. DNA was precipitated with 2-propanol and washed with 70% ethanol. The pellet was dried at room temperature. 10 ml sterile ddH2O was added to the pellet. Then the DNA was treated with 1 ml RNase A (1mg/ml) at 37°C for 30 min. To check the mononucleosomal DNA fragments and MNase digestion level, electrophoresis was carried out on a 2% agarose gel. Samples were further analyzed on a Bioanalyzer 2100 to determine quality prior to library preparation. The libraries were generated using a KAPA library preparation kit (KK8200, Illumina Series). A spike-in control which mimics the size of the mononucleosomal fragment was included during the library construction, and was added according to the number of cells used to isolate the mononucleosomal fragments. The spike-in control used here comprises a set of three DNA sequences that were each around 150 nucleotides in length, with GC contents that mimic the GC% of the S. cerevisiae genome but with no significant similarity to the yeast genome. DNA fragments were size-selected between 200-400 bp after ligation of 121 bp adapters (Next flexTM DNA Barcodes-6). Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143095 gds 301143095 GEO Accession GSM1143095 SRX278564 GSM1143096_1 SRP022854 GSE47023 SRS421416 GSM1143096 MNase-Seq GENOMIC MNase The strains were grown in medium at 30°C overnight. The same number of young, old and histone H3/H4 overexpressing cells were collected and the cells were cross-linked with formaldehyde. The cells were washed twice in 1xPBS buffer and pelleted. Then cells were resuspended in the Zymolyase buffer (1M sorbitol, 50 mM Tris-HCl at pH 7.4, and 10 mM b- Mercaptoethanol) for cell wall digestion with zymolyase-100T. After zymolyase-100T treatment, spheroplasts were pelleted and then resuspended in NP buffer (1M sorbitol, 50 mM NaCl, 10 mM Tris-HCl at pH 7.4, 5 mM MgCl2, 1mM CaCl2 and 0.075% Nonidet P40, and 500 mM spermidine). Micrococcal nuclease (MNase) was added to a final concentration of 1 U MNase/sample. The digestion reactions were incubated at 37°C for 30 min, and were stopped by adding SDS to a final concentration of 1% and EDTA to a final concentration of 10 mM. 5 ml of proteinase K solution was added to each tube. To reverse the formaldehyde cross-links, samples were incubated at 65°C overnight. Samples were extracted with 1 volume phenol/chloroform-IAA and centrifuged at room temperature for 15 min. DNA was precipitated with 2-propanol and washed with 70% ethanol. The pellet was dried at room temperature. 10 ml sterile ddH2O was added to the pellet. Then the DNA was treated with 1 ml RNase A (1mg/ml) at 37°C for 30 min. To check the mononucleosomal DNA fragments and MNase digestion level, electrophoresis was carried out on a 2% agarose gel. Samples were further analyzed on a Bioanalyzer 2100 to determine quality prior to library preparation. The libraries were generated using a KAPA library preparation kit (KK8200, Illumina Series). A spike-in control which mimics the size of the mononucleosomal fragment was included during the library construction, and was added according to the number of cells used to isolate the mononucleosomal fragments. The spike-in control used here comprises a set of three DNA sequences that were each around 150 nucleotides in length, with GC contents that mimic the GC% of the S. cerevisiae genome but with no significant similarity to the yeast genome. DNA fragments were size-selected between 200-400 bp after ligation of 121 bp adapters (Next flexTM DNA Barcodes-6). Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143096 gds 301143096 GEO Accession GSM1143096 SRX278565 GSM1143097_1 SRP022854 GSE47023 SRS421417 GSM1143097 MNase-Seq GENOMIC MNase The strains were grown in medium at 30°C overnight. The same number of young, old and histone H3/H4 overexpressing cells were collected and the cells were cross-linked with formaldehyde. The cells were washed twice in 1xPBS buffer and pelleted. Then cells were resuspended in the Zymolyase buffer (1M sorbitol, 50 mM Tris-HCl at pH 7.4, and 10 mM b- Mercaptoethanol) for cell wall digestion with zymolyase-100T. After zymolyase-100T treatment, spheroplasts were pelleted and then resuspended in NP buffer (1M sorbitol, 50 mM NaCl, 10 mM Tris-HCl at pH 7.4, 5 mM MgCl2, 1mM CaCl2 and 0.075% Nonidet P40, and 500 mM spermidine). Micrococcal nuclease (MNase) was added to a final concentration of 1 U MNase/sample. The digestion reactions were incubated at 37°C for 30 min, and were stopped by adding SDS to a final concentration of 1% and EDTA to a final concentration of 10 mM. 5 ml of proteinase K solution was added to each tube. To reverse the formaldehyde cross-links, samples were incubated at 65°C overnight. Samples were extracted with 1 volume phenol/chloroform-IAA and centrifuged at room temperature for 15 min. DNA was precipitated with 2-propanol and washed with 70% ethanol. The pellet was dried at room temperature. 10 ml sterile ddH2O was added to the pellet. Then the DNA was treated with 1 ml RNase A (1mg/ml) at 37°C for 30 min. To check the mononucleosomal DNA fragments and MNase digestion level, electrophoresis was carried out on a 2% agarose gel. Samples were further analyzed on a Bioanalyzer 2100 to determine quality prior to library preparation. The libraries were generated using a KAPA library preparation kit (KK8200, Illumina Series). A spike-in control which mimics the size of the mononucleosomal fragment was included during the library construction, and was added according to the number of cells used to isolate the mononucleosomal fragments. The spike-in control used here comprises a set of three DNA sequences that were each around 150 nucleotides in length, with GC contents that mimic the GC% of the S. cerevisiae genome but with no significant similarity to the yeast genome. DNA fragments were size-selected between 200-400 bp after ligation of 121 bp adapters (Next flexTM DNA Barcodes-6). Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143097 gds 301143097 GEO Accession GSM1143097 SRX278566 GSM1143098_1 SRP022854 GSE47023 SRS421418 GSM1143098 MNase-Seq GENOMIC MNase The same number of purified young and old cells was subjected to genomic DNA isolation. The masterpureTM yeast DNA purification kit (cat. Nos. MPY80010 and MPY 80200) was used to isolate the genomic DNA. Briefly, 300 ml of yeast cell lysis solution was added to each cell pellet. 1 ml of 5 mg/ml RNase A was added to each pellet. The cells were resuspended and incubated at 65°C for 15 minutes. Samples were placed on ice for 5 minutes. 150 ml MPC protein precipitation reagent was added and vortexed. The cellular debris was pelleted by centrifugation for 10 min at 13,200 rpm. The supernatant was added to 500 ml isopropanol and the DNA was pelleted by centrifugation at 13,200 rpm for 10 minutes. The pellet was washed with 0.5 ml 70% ethanol. The ethanol was removed and the pellet was dried at room temperature. The isolated genomic DNA was fragmented using a Covaris sonicator to mimic the size of mononucleosomal DNA fragments for the size selection. The libraries were generated using a KAPA library preparation kit (KK8200, Illumina Series). During the library construction the same spike-in control described for MNase-seq was included and added proportional to cell number. DNA fragments were size selected between 200-400 bp after ligation of 121 bp adapters. Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143098 gds 301143098 GEO Accession GSM1143098 SRX278567 GSM1143099_1 SRP022854 GSE47023 SRS421419 GSM1143099 MNase-Seq GENOMIC MNase The same number of purified young and old cells was subjected to genomic DNA isolation. The masterpureTM yeast DNA purification kit (cat. Nos. MPY80010 and MPY 80200) was used to isolate the genomic DNA. Briefly, 300 ml of yeast cell lysis solution was added to each cell pellet. 1 ml of 5 mg/ml RNase A was added to each pellet. The cells were resuspended and incubated at 65°C for 15 minutes. Samples were placed on ice for 5 minutes. 150 ml MPC protein precipitation reagent was added and vortexed. The cellular debris was pelleted by centrifugation for 10 min at 13,200 rpm. The supernatant was added to 500 ml isopropanol and the DNA was pelleted by centrifugation at 13,200 rpm for 10 minutes. The pellet was washed with 0.5 ml 70% ethanol. The ethanol was removed and the pellet was dried at room temperature. The isolated genomic DNA was fragmented using a Covaris sonicator to mimic the size of mononucleosomal DNA fragments for the size selection. The libraries were generated using a KAPA library preparation kit (KK8200, Illumina Series). During the library construction the same spike-in control described for MNase-seq was included and added proportional to cell number. DNA fragments were size selected between 200-400 bp after ligation of 121 bp adapters. Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143099 gds 301143099 GEO Accession GSM1143099 SRX278568 GSM1143100_1 SRP022854 GSE47023 SRS421420 GSM1143100 MNase-Seq GENOMIC MNase The same number of purified young and old cells was subjected to genomic DNA isolation. The masterpureTM yeast DNA purification kit (cat. Nos. MPY80010 and MPY 80200) was used to isolate the genomic DNA. Briefly, 300 ml of yeast cell lysis solution was added to each cell pellet. 1 ml of 5 mg/ml RNase A was added to each pellet. The cells were resuspended and incubated at 65°C for 15 minutes. Samples were placed on ice for 5 minutes. 150 ml MPC protein precipitation reagent was added and vortexed. The cellular debris was pelleted by centrifugation for 10 min at 13,200 rpm. The supernatant was added to 500 ml isopropanol and the DNA was pelleted by centrifugation at 13,200 rpm for 10 minutes. The pellet was washed with 0.5 ml 70% ethanol. The ethanol was removed and the pellet was dried at room temperature. The isolated genomic DNA was fragmented using a Covaris sonicator to mimic the size of mononucleosomal DNA fragments for the size selection. The libraries were generated using a KAPA library preparation kit (KK8200, Illumina Series). During the library construction the same spike-in control described for MNase-seq was included and added proportional to cell number. DNA fragments were size selected between 200-400 bp after ligation of 121 bp adapters. Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143100 gds 301143100 GEO Accession GSM1143100 SRX278569 GSM1143101_1 SRP022854 GSE47023 SRS421421 GSM1143101 MNase-Seq GENOMIC MNase The same number of purified young and old cells was subjected to genomic DNA isolation. The masterpureTM yeast DNA purification kit (cat. Nos. MPY80010 and MPY 80200) was used to isolate the genomic DNA. Briefly, 300 ml of yeast cell lysis solution was added to each cell pellet. 1 ml of 5 mg/ml RNase A was added to each pellet. The cells were resuspended and incubated at 65°C for 15 minutes. Samples were placed on ice for 5 minutes. 150 ml MPC protein precipitation reagent was added and vortexed. The cellular debris was pelleted by centrifugation for 10 min at 13,200 rpm. The supernatant was added to 500 ml isopropanol and the DNA was pelleted by centrifugation at 13,200 rpm for 10 minutes. The pellet was washed with 0.5 ml 70% ethanol. The ethanol was removed and the pellet was dried at room temperature. The isolated genomic DNA was fragmented using a Covaris sonicator to mimic the size of mononucleosomal DNA fragments for the size selection. The libraries were generated using a KAPA library preparation kit (KK8200, Illumina Series). During the library construction the same spike-in control described for MNase-seq was included and added proportional to cell number. DNA fragments were size selected between 200-400 bp after ligation of 121 bp adapters. Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143101 gds 301143101 GEO Accession GSM1143101 SRX278570 GSM1143102_1 SRP022854 GSE47023 SRS421422 GSM1143102 RNA-Seq TRANSCRIPTOMIC cDNA Total RNA isolation was performed using the MasterPure Yeast RNA Isolation Kit from Epicentre Biotechnologies (catalog no. MPY03100) following the manufacturer’s instructions. We included the DNase I digestion steps in our RNA isolation to ensure a purer sample for subsequent analyses. The quality of the RNA was confirmed by Agilent 2100 Bioanalyzer electropherograms. The total RNA was spiked-in with the external RNA Controls Consortium (ERCC) spike-in control mixes (Ambion, 4456740) based on the same number of cells for each sample. The ERCC RNA Spike-In Control Mixes used here comprise a set of 92 polyadenylated transcripts that mimic natural eukaryotic mRNAs. The RNAs range in size from 250–2,000 nucleotides in length and span an approximately 106-fold concentration range. Ribosomal RNA was removed using the ribo-zero rRNA removal kit (Epicentre, MRZH11124). cDNA libraries were prepared using the ScriptSeqTM v2 RNA-seq library preparation kit (Epicentre, SSV21106) Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143102 gds 301143102 GEO Accession GSM1143102 SRX278571 GSM1143103_1 SRP022854 GSE47023 SRS421423 GSM1143103 RNA-Seq TRANSCRIPTOMIC cDNA Total RNA isolation was performed using the MasterPure Yeast RNA Isolation Kit from Epicentre Biotechnologies (catalog no. MPY03100) following the manufacturer’s instructions. We included the DNase I digestion steps in our RNA isolation to ensure a purer sample for subsequent analyses. The quality of the RNA was confirmed by Agilent 2100 Bioanalyzer electropherograms. The total RNA was spiked-in with the external RNA Controls Consortium (ERCC) spike-in control mixes (Ambion, 4456740) based on the same number of cells for each sample. The ERCC RNA Spike-In Control Mixes used here comprise a set of 92 polyadenylated transcripts that mimic natural eukaryotic mRNAs. The RNAs range in size from 250–2,000 nucleotides in length and span an approximately 106-fold concentration range. Ribosomal RNA was removed using the ribo-zero rRNA removal kit (Epicentre, MRZH11124). cDNA libraries were prepared using the ScriptSeqTM v2 RNA-seq library preparation kit (Epicentre, SSV21106) Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143103 gds 301143103 GEO Accession GSM1143103 SRX278572 GSM1143104_1 SRP022854 GSE47023 SRS421424 GSM1143104 RNA-Seq TRANSCRIPTOMIC cDNA Total RNA isolation was performed using the MasterPure Yeast RNA Isolation Kit from Epicentre Biotechnologies (catalog no. MPY03100) following the manufacturer’s instructions. We included the DNase I digestion steps in our RNA isolation to ensure a purer sample for subsequent analyses. The quality of the RNA was confirmed by Agilent 2100 Bioanalyzer electropherograms. The total RNA was spiked-in with the external RNA Controls Consortium (ERCC) spike-in control mixes (Ambion, 4456740) based on the same number of cells for each sample. The ERCC RNA Spike-In Control Mixes used here comprise a set of 92 polyadenylated transcripts that mimic natural eukaryotic mRNAs. The RNAs range in size from 250–2,000 nucleotides in length and span an approximately 106-fold concentration range. Ribosomal RNA was removed using the ribo-zero rRNA removal kit (Epicentre, MRZH11124). cDNA libraries were prepared using the ScriptSeqTM v2 RNA-seq library preparation kit (Epicentre, SSV21106) Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143104 gds 301143104 GEO Accession GSM1143104 SRX278573 GSM1143105_1 SRP022854 GSE47023 SRS421425 GSM1143105 RNA-Seq TRANSCRIPTOMIC cDNA Total RNA isolation was performed using the MasterPure Yeast RNA Isolation Kit from Epicentre Biotechnologies (catalog no. MPY03100) following the manufacturer’s instructions. We included the DNase I digestion steps in our RNA isolation to ensure a purer sample for subsequent analyses. The quality of the RNA was confirmed by Agilent 2100 Bioanalyzer electropherograms. The total RNA was spiked-in with the external RNA Controls Consortium (ERCC) spike-in control mixes (Ambion, 4456740) based on the same number of cells for each sample. The ERCC RNA Spike-In Control Mixes used here comprise a set of 92 polyadenylated transcripts that mimic natural eukaryotic mRNAs. The RNAs range in size from 250–2,000 nucleotides in length and span an approximately 106-fold concentration range. Ribosomal RNA was removed using the ribo-zero rRNA removal kit (Epicentre, MRZH11124). cDNA libraries were prepared using the ScriptSeqTM v2 RNA-seq library preparation kit (Epicentre, SSV21106) Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143105 gds 301143105 GEO Accession GSM1143105 SRX278574 GSM1143106_1 SRP022854 GSE47023 SRS421426 GSM1143106 RNA-Seq TRANSCRIPTOMIC cDNA Total RNA isolation was performed using the MasterPure Yeast RNA Isolation Kit from Epicentre Biotechnologies (catalog no. MPY03100) following the manufacturer’s instructions. We included the DNase I digestion steps in our RNA isolation to ensure a purer sample for subsequent analyses. The quality of the RNA was confirmed by Agilent 2100 Bioanalyzer electropherograms. The total RNA was spiked-in with the external RNA Controls Consortium (ERCC) spike-in control mixes (Ambion, 4456740) based on the same number of cells for each sample. The ERCC RNA Spike-In Control Mixes used here comprise a set of 92 polyadenylated transcripts that mimic natural eukaryotic mRNAs. The RNAs range in size from 250–2,000 nucleotides in length and span an approximately 106-fold concentration range. Ribosomal RNA was removed using the ribo-zero rRNA removal kit (Epicentre, MRZH11124). cDNA libraries were prepared using the ScriptSeqTM v2 RNA-seq library preparation kit (Epicentre, SSV21106) Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143106 gds 301143106 GEO Accession GSM1143106 SRX278575 GSM1143107_1 SRP022854 GSE47023 SRS421427 GSM1143107 RNA-Seq TRANSCRIPTOMIC cDNA Total RNA isolation was performed using the MasterPure Yeast RNA Isolation Kit from Epicentre Biotechnologies (catalog no. MPY03100) following the manufacturer’s instructions. We included the DNase I digestion steps in our RNA isolation to ensure a purer sample for subsequent analyses. The quality of the RNA was confirmed by Agilent 2100 Bioanalyzer electropherograms. The total RNA was spiked-in with the external RNA Controls Consortium (ERCC) spike-in control mixes (Ambion, 4456740) based on the same number of cells for each sample. The ERCC RNA Spike-In Control Mixes used here comprise a set of 92 polyadenylated transcripts that mimic natural eukaryotic mRNAs. The RNAs range in size from 250–2,000 nucleotides in length and span an approximately 106-fold concentration range. Ribosomal RNA was removed using the ribo-zero rRNA removal kit (Epicentre, MRZH11124). cDNA libraries were prepared using the ScriptSeqTM v2 RNA-seq library preparation kit (Epicentre, SSV21106) Illumina HiSeq 2000 GEO Sample http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1143107 gds 301143107 GEO Accession GSM1143107