BRWD1 orchestrates epigenetic landscape of late B lymphopoiesis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30250168.
- Also identified by DOI 10.1038/s41467-018-06165-6 and PMC identifier 6155124.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Transcription factor (TF) networks determine cell fate in hematopoiesis. However, how TFs cooperate with other regulatory mechanisms to instruct transcription remains poorly understood. Here we show that in small pre-B cells, the lineage restricted epigenetic reader BRWD1 closes early development enhancers and opens the enhancers of late B lymphopoiesis to TF binding. BRWD1 regulates over 7000 genes to repress proliferative and induce differentiation programs. However, BRWD1 does not regulate the expression of TFs required for B lymphopoiesis. Hypogammaglobulinemia patients with BRWD1 mutations have B-cell transcriptional profiles and enhancer landscapes similar to those observed in Brwd1<sup>-/-</sup> mice. These data indicate that, in both mice and humans, BRWD1 is a master orchestrator of enhancer accessibility that cooperates with TF networks to drive late B-cell development.
Medical subject headings
- Agammaglobulinemia
- Carrier Proteins
- Epigenesis, Genetic
- Lymphopoiesis
- Nuclear Proteins