CHD4 is essential for transcriptional repression and lineage progression in B lymphopoiesis.
Tessa ArendsCarissa DegeAlexandra BortnickLaura D HarmacekJennifer R KnappHaiqun JiaLaura HarmacekCourtney J FleenorDesiree StraignKendra WaltonSonia M LeachAnn J FeeneyCornelis MurreBrian P O'ConnorJames R HagmanPublished in: Proceedings of the National Academy of Sciences of the United States of America (2019)
Cell lineage specification is a tightly regulated process that is dependent on appropriate expression of lineage and developmental stage-specific transcriptional programs. 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 B cell progenitors in vivo, development of these cells is arrested at an early pro-B-like stage that is unresponsive to IL-7 receptor signaling and unable to efficiently complete V(D)J rearrangements at Igh loci. Our studies confirm that chromatin accessibility and transcription of thousands of gene loci are controlled dynamically by CHD4 during early B cell development. Strikingly, CHD4-deficient pro-B cells express transcripts of many non-B cell lineage genes, including genes that are characteristic of other hematopoietic lineages, neuronal cells, and the CNS, lung, pancreas, and other cell types. We conclude that CHD4 inhibits inappropriate transcription in pro-B cells. Together, our data demonstrate the importance of CHD4 in establishing and maintaining an appropriate transcriptome in early B lymphopoiesis via chromatin accessibility.
Keyphrases
- genome wide
- single cell
- transcription factor
- gene expression
- cell fate
- rna seq
- induced apoptosis
- dna methylation
- genome wide identification
- binding protein
- cell cycle arrest
- poor prognosis
- cell therapy
- anti inflammatory
- oxidative stress
- cell proliferation
- quality improvement
- long non coding rna
- machine learning
- stem cells
- subarachnoid hemorrhage
- electronic health record
- cell free
- single molecule
- heat shock protein
- brain injury