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 language | English |
|---|---|
| Pages (from-to) | 901-911 |
| Number of pages | 11 |
| Journal | Molecular Cell |
| Volume | 39 |
| Issue number | 6 |
| DOIs | |
| State | Published - Sep 2010 |
| Externally published | Yes |
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.).