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Title: Control of developmentally primed erythroid genes by combinatorial corepressor actions      
dateReleased:
11-19-2015
description:
How transcription factors (TFs) cooperate within large protein complexes to allow rapid modulation of gene expression during development is still largely unknown. Here we show that the key haematopoietic LIM-domain-binding protein-1 (LDB1) TF complex contains several activator and repressor components that together maintain an erythroid-specific gene expression programme primed for rapid activation until differentiation is induced. A combination of proteomics, functional genomics and in vivo studies presented here identifies known and novel co-repressors, most notably the ETO2 and IRF2BP2 proteins, involved in maintaining this primed state. The ETO2–IRF2BP2 axis, interacting with the NCOR1/SMRT co-repressor complex, suppresses the expression of the vast majority of archetypical erythroid genes and pathways until its decommissioning at the onset of terminal erythroid differentiation. Our experiments demonstrate that multimeric regulatory complexes feature a dynamic interplay between activating and repressing components that determines lineage-specific gene expression and cellular differentiation. ChIP-Sequencing profiles of the IRF2BP2, GFI1B and LSD1 proteins were generated using mouse erythroleukemia (MEL) cells. RNA-seq experiments of Irf2bp2-WT, Irf2bp2-KD, Eto2-WT, Eto2-KD, Gfi1b-WT, Gfi1b-KD, Lsd1-WT, Lsd1-KD, MEL-non-induced, and MEL-induced stages were performed using standard RNA-seq protocol. Illumina HiSeq 2000 (standard TruSeq RNA sequencing protocol) was used for the sequencing.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-59859
refinement:
raw
alternateIdentifiers:
59859
keywords:
functional genomics
dateModified:
11-24-2015
availability:
available
types:
gene expression
name:
Mus musculus
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-59859/E-GEOD-59859.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-59859/E-GEOD-59859.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE59859
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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