Chromatin reorganization drives overexpression of a Btaf1 variant underpinning hematopoietic aging - PubMed
3 hours ago
- #Btaf1 variant
- #chromatin reorganization
- #hematopoietic aging
- Chromatin reorganization in aging hematopoietic stem cells (HSCs) leads to overexpression of a shorter Btaf1 variant (nBtaf1).
- A looping structure between part of the Btaf1 gene and the whole Ide gene is identified in old HSCs, associated with nBtaf1 overexpression.
- nBtaf1 drives aging-associated overexpression of HSC and megakaryocyte progenitor (MkP) signature genes by regulating TBP binding at their promoters.
- This contributes to HSC expansion and elevated MkP production in aged mice.
- ShRNA-mediated knockdown of nBtaf1 restores a younger HSC transcriptome and represses aging-associated HSC expansion and elevated MkP production.
- The study provides high-resolution analysis of dysregulated HSC aging epigenome and identifies nBtaf1 as a driver of HSC aging phenotypes in mice.