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1.
Nucleic Acids Res ; 47(9): 4509-4520, 2019 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-30892634

RESUMEN

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.


Asunto(s)
Envejecimiento/genética , Células Madre Hematopoyéticas/metabolismo , Proteína de la Leucemia Promielocítica con Dedos de Zinc/genética , Transcripción Genética , Animales , Diferenciación Celular/genética , Elementos de Facilitación Genéticos , Epigénesis Genética/genética , Regulación del Desarrollo de la Expresión Génica/genética , Histonas/genética , Humanos , Histona Demetilasas con Dominio de Jumonji/genética , Ratones , Células Progenitoras Mieloides/metabolismo , Unión Proteica , Secuencias Reguladoras de Ácidos Nucleicos/genética
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