Study of mitotic chromatin supports a model of bookmarking by histone modifications and reveals nucleosome deposition patterns

Elisheva Javasky, Inbal Shamir, Shashi Gandhi, Shawn Egri, Oded Sandler, Scott B. Rothbart, Noam Kaplan, Jacob D. Jaffe, Alon Goren*, Itamar Simon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Mitosis encompasses key molecular changes including chromatin condensation, nuclear envelope breakdown, and reduced transcription levels. Immediately after mitosis, the interphase chromatin structure is reestablished and transcription resumes. The reestablishment of the interphase chromatin is probably achieved by "bookmarking," i.e., the retention of at least partial information during mitosis. To gain a deeper understanding of the contribution of histone modifications to the mitotic bookmarking process, we merged proteomics, immunofluorescence, and ChIP-seq approaches. We focused on key histone modifications and employed HeLa-S3 cells as a model system. Generally, in spite of the general hypoacetylation observed during mitosis, we observed a global concordance between the genomic organization of histone modifications in interphase and mitosis, suggesting that the epigenomic landscape may serve as a component of the mitotic bookmarking process. Next, we investigated the nucleosome that enters nucleosome depleted regions (NDRs) during mitosis. We observed that in ∼60% of the NDRs, the entering nucleosome is distinct from the surrounding highly acetylated nucleosomes and appears to have either low levels of acetylation or high levels of phosphorylation in adjacent residues (since adjacent phosphorylation may interfere with the ability to detect acetylation). Inhibition of histone deacetylases (HDACs) by the small molecule TSA reverts this pattern, suggesting that these nucleosomes are specifically deacetylated during mitosis. Altogether, by merging multiple approaches, our study provides evidence to support a model where histone modifications may play a role in mitotic bookmarking and uncovers new insights into the deposition of nucleosomes during mitosis.

Original languageAmerican English
Pages (from-to)1455-1466
Number of pages12
JournalGenome Research
Issue number10
StatePublished - Oct 2018

Bibliographical note

Funding Information:
We thank Dr. Michele Busby and Dr. Melissa Gymrek for fruitful discussions; Yutong Qiu, Miguel Alcantar, and Michal Schlesinger for technical assistance; and Dr. Jason Ernst for assistance with HeLa-S3 ChromHMM data. This research was supported by the Israel Science Foundation (grant no. 184/16 to I.S.), the Israel Science Foundation - Broad Institute Joint Program (grant no. 1972/15 to I.S. and A.G.), the United States-Israel Binational Science Foundation (BSF), Jerusalem, Israel (grant no. 2015272 to I.S. and A.G.), and National Institutes of Health grants (U54 HG008097 to J.D.J. and MIRA R35GM124736 to S.B.R.).

Publisher Copyright:
© 2018 King et al.


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