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| Status |
Public on Apr 30, 2019 |
| Title |
CHD4 is essential for transcriptional repression and lineage progression in B lymphopoiesis [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cell-lineage specification is a tightly regulated process that is dependent on appropriate expression of lineage- and developmental stage-specific transcriptional programs. Accessibility and inaccessibility of gene loci are controlled dynamically during cellular development. Here, we show that Chromodomain Helicase DNA-binding protein 4 (CHD4), a major ATPase/helicase subunit of Nucleosome Remodeling and Deacetylase Complexes (NuRD) in lymphocytes, is essential for specification of the early B cell lineage transcriptional program. In the absence of CHD4 in early B cell progenitors in vivo, B cell progenitors are arrested at an early pro-B-like stage of development, unresponsive to IL-7 receptor signaling and complete V(D)J rearrangements at Igh loci inefficiently. Importantly, CHD4-deficient B cells express a significant number of non-B cell lineage genes, including genes involved in the development of other hematopoietic lineages and neuronal cells. The absence of CHD4 increased chromatin accessibility at hundreds of these gene loci, suggesting that its ability to repress transcription by mobilizing nucleosomes and compacting chromatin is a barrier against inappropriate transcription. Together, our data demonstrate the importance of CHD4 in establishing and maintaining an appropriate transcriptome in early B lymphopoiesis via chromatin accessibility.
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| Overall design |
RNA-seq transcriptome analysis of three independent RNA samples each from wild type or Chd4 conditional knockout pro-B cells.
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| Contributor(s) |
Arends T, Dege C, Bortnick A, Danhorn T, Knapp JR, Jia H, Harmacek L, Fleenor CJ, Straign D, Walton K, Leach SM, Feeney AJ, Murre C, O'Connor BP, Hagman J |
| Citation(s) |
31085655 |
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| Submission date |
Dec 07, 2018 |
| Last update date |
Jul 30, 2019 |
| Contact name |
James R Hagman |
| E-mail(s) |
hagmanj@njhealth.org
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| Phone |
3033981398
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| Organization name |
National Jewish Health
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| Department |
Biomedical Research
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| Lab |
Hagman
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| Street address |
1400 Jackson St
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| City |
Denver |
| State/province |
Colorado |
| ZIP/Postal code |
80206 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE123504 |
CHD4 is essential for transcriptional repression and lineage progression in B lymphopoiesis |
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| Relations |
| BioProject |
PRJNA508956 |
| SRA |
SRP173193 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE123502_subread_genecounts.txt.gz |
3.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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