Polycomb complexes redundantly maintain epidermal stem cell identity during development.
Polycomb complexes redundantly maintain epidermal stem cell identity during development.
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多梳复合体在发育过程中冗余地维持表皮干细胞的特性。
DOI：
10.1101/gad.345363.120
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发表时间：
2021-03-01
影响因子：
10.5
通讯作者：
Ezhkova E
中科院分区：
文献类型：
--
作者：
Cohen I;Bar C;Liu H;Valdes VJ;Zhao D;Galbo PM Jr;Silva JM;Koseki H;Zheng D;Ezhkova E
在这项研究中，科恩等人。试图了解PRC1和PRC2在功能上的贡献，这两个基因在基因组结合上大部分重叠，并合作建立由H2AK119ub和H3K27me3划分的抑制染色质结构域，对基因抑制做出贡献。通过使用发育中的小鼠表皮作为范例，他们发现了Polycomb复合体之间以前未被认识到的功能冗余，他们的发现表明PRC1和PRC2是如何作为两个独立的对应物发挥作用的，提供了一个压抑的安全网，保护和保留了血统认同。多梳抑制复合体1(Prc1)和prc2是重要的表观遗传发育调节因子。PRC1和PRC2在基因组结合上大部分重叠，并合作建立由H2AK119ub和H3K27me3划分的抑制染色质结构域。然而，每个复合体对基因抑制的功能贡献一直是一个争论的主题，理解它的生理意义需要进一步的研究。在这里，使用发育中的小鼠表皮作为范例，我们发现了Polycomb复合体之间以前不为人知的功能冗余。在胚胎表皮祖细胞中切割PRC1和PRC2导致了严重的表皮层积缺陷，这种表型在单个PRC1缺失或PRC2缺失的表皮中没有观察到。分子解剖表明，表皮特性的丧失与非谱系转录因子的强烈去抑制有关，否则在缺乏对应的情况下，被PRC1或PRC2抑制。在野生型表皮干细胞中异位表达PRC1/2抑制的非表皮转录因子亚群足以抑制表皮识别基因，突显了PRC1和PRC2之间功能冗余的重要性。总之，我们的研究表明，PRC1和PRC2是如何作为两个独立的对应物发挥作用的，从而提供了一个保护和保留血统认同的压制性安全网。
In this study, Cohen et al. sought to understand the functional contribution of PRC1 and PRC2, which largely overlap in their genomic binding and cooperate to establish repressive chromatin domains demarcated by H2AK119ub and H3K27me3, to gene repression. By using the developing murine epidermis as a paradigm, they uncovered a previously unappreciated functional redundancy between Polycomb complexes, and their findings show how PRC1 and PRC2 function as two independent counterparts, providing a repressive safety net that protects and preserves lineage identity. Polycomb repressive complex 1 (PRC1) and PRC2 are critical epigenetic developmental regulators. PRC1 and PRC2 largely overlap in their genomic binding and cooperate to establish repressive chromatin domains demarcated by H2AK119ub and H3K27me3. However, the functional contribution of each complex to gene repression has been a subject of debate, and understanding of its physiological significance requires further studies. Here, using the developing murine epidermis as a paradigm, we uncovered a previously unappreciated functional redundancy between Polycomb complexes. Coablation of PRC1 and PRC2 in embryonic epidermal progenitors resulted in severe defects in epidermal stratification, a phenotype not observed in the single PRC1-null or PRC2-null epidermis. Molecular dissection indicated a loss of epidermal identity that was coupled to a strong derepression of nonlineage transcription factors, otherwise repressed by either PRC1 or PRC2 in the absence of its counterpart. Ectopic expression of subsets of PRC1/2-repressed nonepidermal transcription factors in wild-type epidermal stem cells was sufficient to suppress epidermal identity genes, highlighting the importance of functional redundancy between PRC1 and PRC2. Altogether, our studies show how PRC1 and PRC2 function as two independent counterparts, thereby providing a repressive safety net that protects and preserves lineage identity.
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皮肤癌中的 Bmi-1 多聚肌群基因：(-)-表没食子儿茶素-3-棓酸盐对功能的调节。
影响因子：
6.1
作者：
Balasubramanian S;Lee K;Adhikary G;Gopalakrishnan R;Rorke EA;Eckert RL
通讯作者：
Eckert RL
影响因子：
64.5
作者：
Czermin, B;Melfi, R;Pirrotta, V
通讯作者：
Pirrotta, V
影响因子：
8.8
作者：
Cooper S;Dienstbier M;Hassan R;Schermelleh L;Sharif J;Blackledge NP;De Marco V;Elderkin S;Koseki H;Klose R;Heger A;Brockdorff N
通讯作者：
Brockdorff N
DOI：
10.1007/978-1-0716-0648-3_17
发表时间：
2020
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Bar C;Valdes VJ;Ezhkova E
通讯作者：
Ezhkova E
影响因子：
46.9
作者：
Bray, Nicolas L.;Pimentel, Harold;Pachter, Lior
通讯作者：
Pachter, Lior