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Series GSE115357 Query DataSets for GSE115357
Status Public on Dec 31, 2020
Title FBXO11-Mediated Proteolysis of BAHD1 Relieves PRC2-dependent Transcriptional Repression in Erythropoiesis
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary 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 tissue development but poorly understood. Here we show that the E3 ubiquitin ligase FBXO11 relieves PRC2-mediated repression during erythroid maturation by targeting its newly identified substrate BAHD1, an H3K27me3 reader that recruits transcriptional co-repressors. Erythroblasts lacking FBXO11 are developmentally delayed, with reduced expression of maturation-associated genes, most of which harbor bivalent histone marks (activating H3K4me3 and repressive H3K27me3), 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. Previous studies showed that FBXO11 promotes B-cell development and inhibits lymphomagenesis by degrading the transcriptional repressor BCL6. We show that in aggressive B-cell lymphoma lines, depletion of FBXO11 causes the accumulation of both BCL6 and BAHD1, and that suppression of BAHD1 slows cell expansion. Our studies identify BAHD1 as a novel effector of PRC2-mediated repression and reveal how a single E3 ubiquitin ligase eliminates PRC2 repression at developmentally poised bivalent genes during erythropoiesis. The FBXO11-BAHD1 regulatory axis may function in other developmental pathways, including B-lymphopoiesis and lymphomagenesis.
Overall design The goals of this study are to compare the transcriptomes in wild type HUDEP-2 and FBXO11 -/- HUDEP-2 erythroblast. We further compare the transcriptomes in BAHD1shRNA or shLuciferase treated FBXO11 KO HUDEP-2 cells. Finally we intergrate the RNA-seq data with CHIP-Seq data (BAHD1, H3K27me3, H4me3, GATA1) to support our hypothesis.
Contributor(s) Xu P, Xu B, Tang X
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Submission date Jun 05, 2018
Last update date Jan 02, 2021
Contact name Mitch Weiss
Phone 9015953760
Organization name st jude children's research hospital
Department Hematology
Street address 262 Danny Thomas Place
City Memphis
State/province Tennessee
ZIP/Postal code 38105
Country USA
Platforms (3)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (50)
GSM3832643 BAHD1-V5_R1 (ChIP-seq)
GSM3832644 BAHD1-V5_R2 (ChIP-seq)
GSM3832645 BAHD1-V5_R3 (ChIP-seq)
BioProject PRJNA474683
SRA SRP149805

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE115357_RAW.tar 7.2 Gb (http)(custom) TAR (of BW)
GSE115357_RNA.count.all.txt.gz 1.3 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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