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 Detalle_Publicacion

The HDAC7-TET2 epigenetic axis is essential during early B lymphocyte development

Abstract: Correct B cell identity at each stage of cellular differentiation during B lymphocyte development is critically dependent on a tightly controlled epigenomic landscape. We previously identified HDAC7 as an essential regulator of early B cell development and its absence leads to a drastic block at the pro-B to pre-B cell transition. More recently, we demonstrated that HDAC7 loss in pro-B-ALL in infants associates with a worse prognosis. Here we delineate the molecular mechanisms by which HDAC7 modulates early B cell development. We find that HDAC7 deficiency drives global chromatin de-condensation, histone marks deposition and deregulates other epigenetic regulators and mobile elements. Specifically, the absence of HDAC7 induces TET2 expression, which promotes DNA 5-hydroxymethylation and chromatin de-condensation. HDAC7 deficiency also results in the aberrant expression of microRNAs and LINE-1 transposable elements. These findings shed light on the mechanisms by which HDAC7 loss or misregulation may lead to B cell-based hematological malignancies.

 Fuente: Nucleic Acids Research, 2022, Vol. 50, No. 15 8471-8490

Editorial: Oxford University Press

 Fecha de publicación: 29/07/2022

Nº de páginas: 20

Tipo de publicación: Artículo de Revista

 DOI: 10.1093/nar/gkac619

ISSN: 0305-1048,1362-4962

Proyecto español: SAF2017-87990-R, EUR2019-103835

Url de la publicación: https://doi.org/10.1093/nar/gkac619

Autores/as

AZAGRA, ALBA

MELER, AINARA

BARRIOS, ORIOL DE

TOMÁS-DAZA, LAUREANO

OBIOLS, MIREIA

ROVIROSA, LLORENÇ

VILA-CASADESÚS, MARÍA

CABRERA-PASADAS, MÓNICA

GUSI-VIVES, MAR

GRAF, THOMAS

SARDINA, JOSÉ LUIS

JAVIERRE, BIOLA M.

PARRA, MARIBEL