Nuclear DEK preserves hematopoietic stem cells potential via NCoR1/HDAC3-Akt1/2-mTOR axis.

ABSTRACT: The oncogene DEK is found fused with the NUP214 gene creating oncoprotein DEK-NUP214 that induces acute myeloid leukemia (AML) in patients, and secreted DEK protein functions as a hematopoietic cytokine to regulate hematopoiesis; however, the intrinsic role of nuclear DEK in hematopoietic stem cells (HSCs) remains largely unknown. Here, we show that HSCs lacking DEK display defects in long-term self-renew capacity, eventually resulting in impaired hematopoiesis. DEK deficiency reduces quiescence and accelerates mitochondrial metabolism in HSCs, in part, dependent upon activating mTOR signaling. At the molecular level, DEK recruits the corepressor NCoR1 to repress acetylation of histone 3 at lysine 27 (H3K27ac) and restricts the chromatin accessibility of HSCs, governing the expression of q

SUBMITTER: Chen Z 

PROVIDER: S-EPMC7992411 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature