Distinct PRC2 subunits regulate maintenance and establishment of Polycomb repression during differentiation.
Distinct PRC2 subunits regulate maintenance and establishment of Polycomb repression during differentiation.
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DOI：
10.1016/j.molcel.2021.03.038
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发表时间：
2021-06-17
期刊：
影响因子：
16
通讯作者：
Bonasio R
中科院分区：
文献类型：
--
作者：
Petracovici A;Bonasio R
The Polycomb repressive complex 2 (PRC2) is an essential epigenetic regulator that deposits repressive H3K27me3. PRC2 subunits form two holocomplexes—PRC2.1 and PRC2.2—but the roles of these two PRC2 assemblies during differentiation are unclear. We employed auxin-inducible degradation to deplete PRC2.1 subunit MTF2 or PRC2.2 subunit JARID2 during differentiation of embryonic stem cells (ESCs) to neural progenitors (NPCs). Depletion of either MTF2 or JARID2 resulted in incomplete differentiation due to defects in gene regulation. Distinct sets of Polycomb target genes were derepressed in absence of MTF2 or JARID2. MTF2-sensitive genes were marked by H3K27me3 in ESCs and remained silent during differentiation, whereas JARID2-sensitive genes were preferentially active in ESCs and became newly repressed in NPCs. Thus, MTF2 and JARID2 contribute non-redundantly to Polycomb silencing, suggesting that PRC2.1 and PRC2.2 have distinct functions in maintaining and establishing, respectively, Polycomb repression during differentiation. Petracovici et. al employ inducible protein degradation to dissect the functions of subunits specific to the PRC2 holocomplexes PRC2.1 and PRC2.2 during differentiation. They uncover that PRC2.1 and PRC2.2 subunits regulate different gene sets with distinct chromatin and expression dynamics, suggesting underlying functional differences in maintaining and establishing Polycomb repression.
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