CUX1 recruits SWI/SNF to promote chromatin accessibility in human hematopoietic cells

ABSTRACT: Transcription factors(TF) plays a key role in hematopoiesis via promoting cell-type specific gene expression. A subset of TFs, canonically termed “pioneer factors”, possesses the ability to bind to otherwise inaccessible heterochromatin regions, and recruit additional TFs, co-activators, and chromatin remodelers to establish activating/repressive cis-regulatory elements(CRE). To date, few of these TFs with pioneer activity has been elucidated in hematopoiesis. CUX1, a homeobox containing TF frequently mutated in a range of hematological malignancies, has been reported to regulate essential cellular processes and regulate myeloid vs erythroid differentiation. However, the molecular mechanism governing its transcriptional function remains unclear. Using a multi-faceted functional genomic approach, we discovered that CUX1 interacts and recruits the chromatin remodeler SWI/SNF to distal enhancers in both lymphoblast K562 cell line and primary human HSPC. The interaction promotes an accessible state of chromatin, changes in nucleosome positioning and transcriptional programs. We also discovered that the CUX1 & SWI/SNF binding sites are co-occupied by other hematopoietic transcriptional factors. Together this revealed a unique mechanism of CUX1’s regulatory function in hematopoietic development: it recruits SWI/SNF chromatin remodeler to distal enhancers, establish an accessible chromatin landscape and enabled other hematopoietic TFs to bind and activates cell-type specific gene expression programs.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Cell Culture

DISEASE(S): Chronic Myeloid Leukemia

SUBMITTER: Donald Wolfgeher  

LAB HEAD: Dr. Megan E. McNerney M.D.Ph.D.

PROVIDER: PXD037838 | Pride | 2026-03-16

REPOSITORIES: Pride