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Página principal > Artículos > Artículos publicados > The HDAC7-TET2 epigenetic axis is essential during early B lymphocyte development |
Fecha: | 2022 |
Resumen: | 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. |
Ayudas: | Ministerio de Ciencia e Innovación FJCI-2017-32430 Agència de Gestió d'Ajuts Universitaris i de Recerca 2019FI-B00017 Ministerio de Economía y Competitividad SAF2017-87990-R Ministerio de Ciencia e Innovación PRE2019-088005 Instituto de Salud Carlos III CP19/00176 Ministerio de Ciencia e Innovación EUR2019-103835 Agencia Estatal de Investigación PRE2018- 083183 Agencia Estatal de Investigación PID2019-111243RA-I00 Agencia Estatal de Investigación RTI2018-094788-A-I00 |
Nota: | Spanish Ministry of Economy and Competitiveness (MINECO) [SAF2017-87990-R]; Spanish Ministry of Science and Innovation (MICINN) [EUR2019-103835]; Josep Carreras Leukaemia Research Institute (IJC, Badalona, Barcelona); IDIBELL Research Institute (L'Hospitalet de Llobregat, Barcelona); A.M. is funded by the SpanishMinistry of Science, Innovation and Universities, which is part of the Agencia Estatal de Investigación (AEI) [PRE2018- 083183] (cofunded by the European Social Fund]; OdB. was funded by a Juan de la Cierva Formación Fellowship from the Spanish Ministry of Science, Innovation and Universities [FJCI-2017-32430]; Postdoctoral Fellowship from the Asociación Española Contra el Cáncer (AECC) Foundation [POSTD20024DEBA]; B.M. is awardee of the Ayudas para la formación del profesorado universitario [FPU18/00755, Ministerio de Universidades]; B.M.J. is funded by La Caixa Banking Foundation Junior Leader project [LCF/BQ/PI19/11690001]; FEDER/SpanishMinistry of Science and Innovation [RTI2018-094788-A-I00]; L.T.-D. is funded by the FPI Fellowship [PRE2019- 088005]; L.R. is funded by an AGAUR FI fellowship [2019FI-B00017]; J.L.S. is funded by ISCIII [CP19/00176], co-funded by ESF, 'Investing in your future' and the Spanish Ministry of Science, Innovation and Universities [PID2019-111243RA-I00]. CRG acknowledge the support of the SpanishMinistry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049- S, MCIN/AEI /10.13039/501100011033). Funding for open access charge: Spanish Ministry of Science, Innovation and Universities (MICIU) [SAF2017-87990-R, EUR2019-103835]. |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Publicado en: | Nucleic acids research, Vol. 50 Núm. 15 (26 2022) , p. 8471-8490, ISSN 1362-4962 |
20 p, 3.2 MB |