TRIM66-HP1γremodels the chromatin through phase separation  

作　　者：Siyuan Shen Feng Chen Yifan Zhang Fudong Li Xuebiao Yao Dan Liu Yunyu Shi Liang Zhang 

机构地区：[1]Center for Advanced Interdisciplinary Science and Biomedicine of IHM,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230027,China [2]Ministry of Education Key Laboratory for Membraneless Organelles and Cellular Dynamics,University of Science and Technology of China,Hefei 230027,China [3]Hefei National Research Center for Cross disciplinary Science,University of Science and Technology of China,Hefei 230027,China

出　　处：《Biophysics Reports》2025年第1期18-33,共16页生物物理学报(英文版)

基　　金：supported by the National Natural Science Foundation of China(32090040,32293213,92149302 and 32470817);the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB37010105 and XDB39010300);the Fundamental Research Funds for the Central Universities(WK9100000067)。

摘　　要：Chromatin contains not only heterochromatin(HC)and euchromatins(EC)but also facultative heterochromatin(f HC),which experience the dynamic remodeling between HCs and ECs by different regulators.The regulation of f HCs involves lots of different cell functions,like genomic stability and gene transcription.Heterochromatin protein 1(HP1)recognizes methylated H3K9 and reshapes the chromatin into the f HCs through liquid-liquid phase separation(LLPS).Among the three members of the HP1 family,HP1αcan condensate by itself and HP1βforms granules with the help of TRIM28,while the HP1γcannot phase separation alone either and the coordinator is still unclear.So,in this study,we investigated the molecular mechanism of how HP1γinteracts with TRIM66 through Px Vx L motif.Based on that,we examined the key regions that controlled the TRIM66-HP1γco-phase separation behaviors both in vitro and in vivo.Furthermore,we proved that the liquid granules of TRIM66-HP1γand chromatin highly correlated with H3K9me3 sites,which indicated the relationship with DNA damage response.Finally,combined with our previous study,we proposed the system for how TRIM66 remodeled the chromatin into compressed f HC through the TRIM66-HP1γ-H3K9me3 axis with liquid-liquid phase separation.

关 键 词：CHROMATIN TRIM66-HP1γ Facultative heterochromatin Phase separation 

分 类 号：Q343.2[生物学—遗传学]