PLZF limits enhancer activity during hematopoietic progenitor aging | Zendy

Mathilde Poplineau | Zendy; Julien Vernerey | Zendy; Nadine Platet | Zendy; Lia N’Guyen | Zendy; Léonard Hérault | Zendy; Michela Esposito | Zendy; Andrew J. Saurin | Zendy; Christel Guilouf | Zendy; Atsushi Iwama | Zendy; Estelle Duprez | Zendy

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PLZF limits enhancer activity during hematopoietic progenitor aging

Author(s) -

Mathilde Poplineau,

Julien Vernerey,

Nadine Platet,

Lia N’Guyen,

Léonard Hérault,

Michela Esposito,

Andrew J. Saurin,

Christel Guilouf,

Atsushi Iwama,

Estelle Duprez

Publication year - 2019

Publication title -

nucleic acids research

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 9.008

H-Index - 537

eISSN - 1362-4954

pISSN - 0305-1048

DOI - 10.1093/nar/gkz174

Subject(s) - biology , epigenome , enhancer , epigenetics , chromatin , haematopoiesis , transcription factor , histone , chromatin remodeling , microbiology and biotechnology , sirtuin , myeloid , genetics , acetylation , dna methylation , cancer research , stem cell , gene expression , gene

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 toward 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.

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