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FBXO11-mediated proteolysis of BAHD1 relieves PRC2-dependent transcriptional repression in erythropoiesis
- Source :
- Blood
- Publication Year :
- 2021
-
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.
- Subjects :
- 0301 basic medicine
Protein-Arginine N-Methyltransferases
Erythroblasts
Chromosomal Proteins, Non-Histone
Immunology
macromolecular substances
Biochemistry
Cell Line
03 medical and health sciences
0302 clinical medicine
Humans
Erythropoiesis
Psychological repression
biology
Effector
F-Box Proteins
Polycomb Repressive Complex 2
GATA1
Promoter
Cell Biology
Hematology
Cell biology
Ubiquitin ligase
030104 developmental biology
Histone
Gene Expression Regulation
Proteolysis
biology.protein
H3K4me3
PRC2
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 00064971
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....01804c609240eaff7bf88ccc3afedab3
- Full Text :
- https://doi.org/10.1182/blood.2020007809