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Peer-reviewedCC BYNucleic Acids Research

Region-specific generation and retention of acetylated cohesin shape the genome-wide pattern of sister chromatid cohesion

5 affiliations
  1. 1Institute for Quantitative Biosciences, The University of Tokyo , 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032 ,
  2. 2Faculty of Core Research, Natural Sciences Division, Ochanomizu University , 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610 ,
  3. 3Institute of Medical Genetics, Tokyo Women’s Medical University , 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 ,
  4. 4Department of Cell and Molecular Biology, Karolinska Institutet, Biomedicum , Tomtebodavägen 16, 171 77 Stockholm ,
  5. 5Division of Biological Sciences, Graduate School of Science, Kyoto University , Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 ,

Abstract

Sister chromatid cohesion depends on ESCO2-mediated acetylation of the cohesin subunit SMC3, yet how this modification is established and maintained across the genome remains poorly understood. Here, we examined the chromatin-binding dynamics of ESCO2 and its enzymatic activity using quantitative ChIP-seq of human cells synchronously progressing through S phase. ESCO2 bound broadly along chromosomes without forming discrete peaks and preferentially localized to transcriptionally inactive regions, but was not confined to H3K9me3- or H3K27me3-enriched heterochromatin. Consistent with this binding pattern, ESCO2-dependent SMC3 acetylation showed a similarly broad distribution in these regions. In contrast, ESCO1, a paralog of ESCO2, primarily mediated SMC3 acetylation at cohesin peak sites. Notably, most of the broadly distributed, ESCO2-dependent SMC3 acetylation generated during S phase was progressively lost from chromatin after replication, whereas the fraction that persisted into late G2 accumulated in domains enriched for the repressive H3K27me3 modification. Our work identifies selective post-replicative retention of acetylated cohesin as a previously unappreciated step in shaping the genome-wide architecture of sister chromatid cohesion.

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BibTeX
@article{shimizu2026regionspecific,
  title = {{Region-specific generation and retention of acetylated cohesin shape the genome-wide pattern of sister chromatid cohesion}},
  author = {Mai I Shimizu and Masashige Bando and Atsunori Yoshimura and Toyonori Sakata and Tomoko Nishiyama and Katsuhiko Shirahige and Takashi Sutani},
  journal = {Nucleic Acids Research},
  year = {2026},
  month = oct,
  doi = {10.1093/nar/gkag1061},
  url = {https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1061/9005799},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Region-specific generation and retention of acetylated cohesin shape the genome-wide pattern of sister chromatid cohesion
AU  - Mai I Shimizu
AU  - Masashige Bando
AU  - Atsunori Yoshimura
AU  - Toyonori Sakata
AU  - Tomoko Nishiyama
AU  - Katsuhiko Shirahige
AU  - Takashi Sutani
PY  - 2026
DA  - 2026/10/31
JO  - Nucleic Acids Research
DO  - 10.1093/nar/gkag1061
UR  - https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1061/9005799
AB  - Sister chromatid cohesion depends on ESCO2-mediated acetylation of the cohesin subunit SMC3, yet how this modification is established and maintained across the genome remains poorly understood. Here, we examined the chromatin-binding dynamics of ESCO2 and its enzymatic activity using quantitative ChIP-seq of human cells synchronously progressing through S phase. ESCO2 bound broadly along chromosomes without forming discrete peaks and preferentially localized to transcriptionally inactive regions, but was not confined to H3K9me3- or H3K27me3-enriched heterochromatin. Consistent with this binding pattern, ESCO2-dependent SMC3 acetylation showed a similarly broad distribution in these regions. In contrast, ESCO1, a paralog of ESCO2, primarily mediated SMC3 acetylation at cohesin peak sites. Notably, most of the broadly distributed, ESCO2-dependent SMC3 acetylation generated during S phase was progressively lost from chromatin after replication, whereas the fraction that persisted into late G2 accumulated in domains enriched for the repressive H3K27me3 modification. Our work identifies selective post-replicative retention of acetylated cohesin as a previously unappreciated step in shaping the genome-wide architecture of sister chromatid cohesion.
SN  - 0305-1048
SN  - 1362-4962
ER  -