PLZF limits enhancer activity during hematopoietic progenitor aging

PLZF (promyelocytic leukemia zinc finger) is a transcription factor acting as a global regulator of hematopoietic commitment. PLZF displays an epigenetic specificity by recruiting chromatin-modifying factors but little is known about its role in remodeling chromatin of cells committed towards a given specific hematopoietic lineage. In murine myeloid progenitors, we decipher a new role for PLZF in restraining active genes and enhancers by targeting acetylated lysine 27 of Histone H3 (H3K27ac). Functional analyses reveal that active enhancers bound by PLZF are involved in biological processes related to metabolism and associated with hematopoietic aging. Comparing the epigenome of young and old myeloid progenitors, we reveal that H3K27ac variation at active enhancers is a hallmark of hematopoietic aging. Taken together, these data suggest that PLZF, associated with active enhancers, appears to restrain their activity as an epigenetic gatekeeper of hematopoietic aging. Overall design: ChIP-seq for PLZF-Flag and input on 416b cells transduced by PLZF-Flag or empty vector. ChIP-seq for H3K4me3, H3K4me1, H3K27me3, H3K27ac and input on 416b transduced by PLZF-Flag or empty vector. RNA-seq performed on total RNA purified from 416b transduced by PLZF-Flag or empty vector. ATAC-seq performed on genomic DNA purified from 416b transduced by PLZF-Flag or empty vector. ChIP-seq for H3K4me3, H3K4me1, H3K27me3, H3K27ac and input on WT and Zbtb16lu/lu GMPs, young GMPs and old GMPs. RNA-seq performed on total RNA purified from primary graft of WT and Zbtb16lu/lu GMPs.