The Chromatin Remodeler BPTF Activates a Stemness Gene-Expression Program Essential for the Maintenance of Adult Hematopoietic Stem Cells

Bowen Xu, Ling Cai, Jason M. Butler, Dongliang Chen, Xiongdong Lu, David F. Allison, Rui Lu, Shahin Rafii, Joel S. Parker, Deyou Zheng, Gang Greg Wang

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Self-renewal and differentiation of adult stem cells are tightly regulated partly through configuration of chromatin structure by chromatin remodelers. Using knockout mice, we here demonstrate that bromodomain PHD finger transcription factor (BPTF), a component of the nucleosome remodeling factor (NURF) chromatin-remodeling complex, is essential for maintaining the population size of hematopoietic stem/progenitor cells (HSPCs), including long-term hematopoietic stem cells (HSCs). Bptf-deficient HSCs are defective in reconstituted hematopoiesis, and hematopoietic-specific knockout of Bptf caused profound defects including bone marrow failure and anemia. Genome-wide transcriptome profiling revealed that BPTF loss caused downregulation of HSC-specific gene-expression programs, which contain several master transcription factors (Meis1, Pbx1, Mn1, and Lmo2) required for HSC maintenance and self-renewal. Furthermore, we show that BPTF potentiates the chromatin accessibility of key HSC “stemness” genes. These results demonstrate an essential requirement of the chromatin remodeler BPTF and NURF for activation of “stemness” gene-expression programs and proper function of adult HSCs. Wang and colleagues show that a chromatin remodeler, BPTF, sustains appropriate functions of hematopoietic stem/progenitor cells (HSPCs). BPTF loss causes bone marrow failure and anemia. The authors further define a BPTF-dependent gene-expression program in HSPCs, which contains key HSC stemness factors. These results demonstrate an essential requirement of the BPTF-associated chromatin remodelers for HSC functionality and adult hematopoiesis.

Original languageEnglish (US)
Pages (from-to)675-683
Number of pages9
JournalStem Cell Reports
Volume10
Issue number3
DOIs
StatePublished - Mar 13 2018

Keywords

  • AP1 complex
  • Bptf
  • DNA accessibility
  • Meis1
  • Mn1
  • NURF
  • Pbx1
  • chromatin remodeler
  • hematopoietic stem cells

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Xu, B., Cai, L., Butler, J. M., Chen, D., Lu, X., Allison, D. F., Lu, R., Rafii, S., Parker, J. S., Zheng, D., & Wang, G. G. (2018). The Chromatin Remodeler BPTF Activates a Stemness Gene-Expression Program Essential for the Maintenance of Adult Hematopoietic Stem Cells. Stem Cell Reports, 10(3), 675-683. https://doi.org/10.1016/j.stemcr.2018.01.020