H2A.Z maintenance during mitosis reveals nucleosome shifting on mitotically silenced genes

Theresa K. Kelly, Tina Branscombe Miranda, Gangning Liang, Benjamin P. Berman, Joy C. Lin, Amos Tanay, Peter A. Jones*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

Profound chromatin changes occur during mitosis to allow for gene silencing and chromosome segregation followed by reactivation of memorized transcription states in daughter cells. Using genome-wide sequencing, we found H2A.Z-containing +1 nucleosomes of active genes shift upstream to occupy TSSs during mitosis, significantly reducing nucleosome-depleted regions. Single-molecule analysis confirmed nucleosome shifting and demonstrated that mitotic shifting is specific to active genes that are silenced during mitosis and, thus, is not seen on promoters, which are silenced by methylation or mitotically expressed genes. Using the GRP78 promoter as a model, we found H3K4 trimethylation is also maintained while other indicators of active chromatin are lost and expression is decreased. These key changes provide a potential mechanism for rapid silencing and reactivation of genes during the cell cycle.

Original languageAmerican English
Pages (from-to)901-911
Number of pages11
JournalMolecular Cell
Volume39
Issue number6
DOIs
StatePublished - Sep 2010
Externally publishedYes

Bibliographical note

Funding Information:
We would like to thank Phillippa Taberlay, Shinwu Jeong, and Erika Wolff and Daniel DeCarvalho for helpful discussions and careful reading of the manuscript. We would like to thank Bradley Bernstein for helpful conversations and Joseph Aman for technical assistance. The ChIP-seq experiments were performed in conjunction with the USC Epigenome center. We would like to thank Mark Miranda for creating the CpG Bubble Chart Generator Program. This work was funded by the US National Institutes of Health grants R37 CA082422 (P.A.J.) and T32 CA009320 (T.K.K.).

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