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Tet1-dependent chromocenter clustering in DNA hypomethylated cells

萩原, 遥太 大阪大学 DOI:10.18910/82351

2021.03.24

概要

Pericentromeric heterochromatin (PCH), constitutive heterochromatin of pericentric regions, plays crucial roles in various cellular events, such as cell division and DNA replication. PCH forms chromocenters in the interphase nucleus and chromocenters further cluster at the prophase of meiosis. This chromocenter clustering has been reported to be critical for normal meiosis progression, especially for synapsis formation. However, the underlying molecular mechanism of chromocenter clustering remains elusive. In this study, I found that global DNA hypomethylation, 5hmC enrichment in PCH, and chromocenter clustering of Dnmt1-KO ESCs were similar to those of female meiotic germ cells. I revealed Tet1 was essential for the deposition of facultative histone marks of H3K27me3 and H2AK119ub at PCH and the chromocenter clustering in Dnmt1-KO ESCs. In this situation, RING1B, one of the core components of PRC1 was recruited to PCH by Tet1 and PRC1 played a critical role in the chromocenter clustering. Rearrangement of chromocenter under the hypomethylated condition was mediated by liquid-liquid phase separation in Dnmt1-KO ESCs. I also found Tet1-KO mice showed chromocenter clustering abnormality at the meiotic prophase. Therefore, I demonstrated a novel role of Tet1 in the chromocenter rearrangement in DNA hypomethylated cells.

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