FBXO11-mediated Proteolysis of BAHD1 Relieves PRC2-dependent Transcriptional Repression in Erythropoiesis

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2020 Nov 6

PMID 33156908

Citations 14

Authors

Peng Xu

Daniel C Scott

Beisi Xu

Yu Yao

Ruopeng Feng

Li Cheng

Kalin Mayberry

Yong-Dong Wang

Wenjian Bi

Lance E Palmer

Moeko T King

Hong Wang

Yuxin Li

Yiping Fan

Arno F Alpi

Chunliang Li

Junmin Peng

James Papizan

Shondra M Pruett-Miller

Ria Spallek

Florian Bassermann

Yong Cheng

Brenda A Schulman

Mitchell J Weiss

Affiliations

Soon will be listed here.

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.

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