RT Journal Article
SR Electronic
T1 Simultaneous Epigenetic Perturbation and Genome Imaging Reveal Distinct Roles of H3K9me3 in Chromatin Architecture and Transcription
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.15.204719
DO 10.1101/2020.07.15.204719
A1 Ying Feng
A1 Yao Wang
A1 Xiangnan Wang
A1 Xiaohui He
A1 Chen Yang
A1 Ardalan Naseri
A1 Thoru Pederson
A1 Jing Zheng
A1 Shaojie Zhang
A1 Xiao Xiao
A1 Wei Xie
A1 Hanhui Ma
YR 2020
UL http://biorxiv.org/content/early/2020/07/16/2020.07.15.204719.abstract
AB Despite the long-observed correlation between H3K9me3, chromatin architecture and transcriptional repression, how H3K9me3 regulates genome higher-order organization and transcriptional activity in living cells remains unclear. Here we develop EpiGo (Epigenetic perturbation induced Genome organization)-KRAB to introduce H3K9me3 at hundreds of loci spanning megabases on human chromosome 19 and simultaneously track genome organization. EpiGo-KRAB is sufficient to induce de novo heterochromatin-like domain formation, which requires SETDB1, a methyltransferase of H3K9me3. Unexpectedly, EpiGo-KRAB induced heterochromatin-like domain does not result in widespread gene repression except a small set of genes with concurrent loss of H3K4me3 and H3K27ac. Ectopic H3K9me3 appears to spread in inactive regions but is largely restricted to transcriptional initiation sites in active regions. Finally, Hi-C analysis showed that EpiGo-KRAB induced to reshape existing compartments. These results reveal the role of H3K9me3 in genome organization could be partially separated from its function in gene repression.Competing Interest StatementThe authors have declared no competing interest.