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Leukemia. 2019 Mar 11. doi: 10.1038/s41375-019-0438-4. [Epub ahead of print]

Chromatin remodeling mediated by ARID1A is indispensable for normal hematopoiesis in mice.

Author information

1
Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
2
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
3
Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. csivm@nus.edu.sg.
4
Department of Cardiac Surgery, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI, USA.
5
Cedars-Sinai Medical Center, Division of Hematology/Oncology, UCLA School of Medicine, Los Angeles, CA, USA.
6
Department of Hematology-Oncology, National University Cancer Institute of Singapore (NCIS), National University Hospital, Singapore, Singapore.

Abstract

Precise regulation of chromatin architecture is vital to physiological processes including hematopoiesis. ARID1A is a core component of the mammalian SWI/SNF complex, which is one of the ATP-dependent chromatin remodeling complexes. To uncover the role of ARID1A in hematopoietic development, we utilized hematopoietic cell-specific deletion of Arid1a in mice. We demonstrate that ARID1A is essential for maintaining the frequency and function of hematopoietic stem cells and its loss impairs the differentiation of both myeloid and lymphoid lineages. ARID1A deficiency led to a global reduction in open chromatin and ensuing transcriptional changes affected key genes involved in hematopoietic development. We also observed that silencing of ARID1A affected ATRA-induced differentiation of NB4 cells, suggesting its role in granulocytic differentiation of human leukemic cells. Overall, our study provides a comprehensive elucidation of the function of ARID1A in hematopoiesis and highlights the central role of ARID1A-containing SWI/SNF complex in maintaining chromatin dynamics in hematopoietic cells.

PMID:
30858552
DOI:
10.1038/s41375-019-0438-4

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