RRC ID 69373
著者 Xu P, Scott DC, Xu B, Yao Y, Feng R, Cheng L, Mayberry K, Wang YD, Bi W, Palmer LE, King MT, Wang H, Li Y, Fan Y, Alpi AF, Li C, Peng J, Papizan J, Pruett-Miller SM, Spallek R, Bassermann F, Cheng Y, Schulman BA, Weiss MJ.
タイトル FBXO11-mediated proteolysis of BAHD1 relieves PRC2-dependent transcriptional repression in erythropoiesis.
ジャーナル Blood
Abstract The histone mark H3K27me3 and its reader/writer polycomb repressive complex 2 (PRC2) mediate widespread transcriptional repression in stem and progenitor cells. Mechanisms that regulate this activity are critical for hematopoietic development but are poorly understood. Here we show that the E3 ubiquitin ligase F-box only protein 11 (FBXO11) relieves PRC2-mediated repression during erythroid maturation by targeting its newly identified substrate bromo adjacent homology domain-containing 1 (BAHD1), an H3K27me3 reader that recruits transcriptional corepressors. Erythroblasts lacking FBXO11 are developmentally delayed, with reduced expression of maturation-associated genes, most of which harbor bivalent histone marks at their promoters. In FBXO11-/- erythroblasts, these gene promoters bind BAHD1 and fail to recruit the erythroid transcription factor GATA1. The BAHD1 complex interacts physically with PRC2, and depletion of either component restores FBXO11-deficient erythroid gene expression. Our studies identify BAHD1 as a novel effector of PRC2-mediated repression and reveal how a single E3 ubiquitin ligase eliminates PRC2 repression at many developmentally poised bivalent genes during erythropoiesis.
巻・号 137(2)
ページ 155-167
公開日 2021-1-14
DOI 10.1182/blood.2020007809
PII S0006-4971(21)00021-5
PMID 33156908
PMC PMC7820877
MeSH Cell Line Chromosomal Proteins, Non-Histone / metabolism* Erythroblasts / metabolism Erythropoiesis / physiology* F-Box Proteins / metabolism* Gene Expression Regulation / physiology* Humans Polycomb Repressive Complex 2 / metabolism* Protein-Arginine N-Methyltransferases / metabolism* Proteolysis
IF 17.794
リソース情報
ヒト・動物細胞 HUDEP-2(RCB4557)