The HDAC7-TET2 epigenetic axis is essential during early B lymphocyte development
Por:
Azagra, A, Meler, A, de Barrios, O, Tomas-Daza, L, Collazo, O, Monterde, B, Obiols, M, Rovirosa, L, Vila-Casadesus, M, Cabrera-Pasadas, M, Gusi-Vives, M, Graf, T, Varela, I, Sardina, JL, Javierre, BM and Parra, M
Publicada:
26 ago 2022
Ahead of Print:
1 jul 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.
Filiaciones:
:
Josep Carreras Leukaemia Res Inst, Lymphocyte Dev & Dis Grp, Badalona 08916, Spain
Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Cellular Differentiat Grp, Av Gran Via 199, Barcelona 08908, Spain
:
Josep Carreras Leukaemia Res Inst, Lymphocyte Dev & Dis Grp, Badalona 08916, Spain
Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Cellular Differentiat Grp, Av Gran Via 199, Barcelona 08908, Spain
:
Josep Carreras Leukaemia Res Inst, Lymphocyte Dev & Dis Grp, Badalona 08916, Spain
Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Cellular Differentiat Grp, Av Gran Via 199, Barcelona 08908, Spain
:
Josep Carreras Leukaemia Res Inst, 3D Chromatin Org Grp, Badalona 08916, Spain
Barcelona Supercomp Ctr BSC, Barcelona, Spain
Collazo, O:
Josep Carreras Leukaemia Res Inst, Lymphocyte Dev & Dis Grp, Badalona 08916, Spain
Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Cellular Differentiat Grp, Av Gran Via 199, Barcelona 08908, Spain
Monterde, B:
Univ Cantabria, Inst Biomed & Biotecnol Cantabria, CSIC, Santander 39011, Spain
Obiols, M:
Josep Carreras Leukaemia Res Inst, Epigenet Control Haematopoiesis Grp, Badalona 08916, Spain
:
Josep Carreras Leukaemia Res Inst, 3D Chromatin Org Grp, Badalona 08916, Spain
Vila-Casadesus, M:
Ctr Genom Regulat CRG, PRBB Bldg,Dr Aiguader 88, Barcelona 08003, Spain
CIBER Hepat & Digest Dis CTBERehd, Bioinformat Platform, Barcelona 08036, Catalonia, Spain
Cabrera-Pasadas, M:
Josep Carreras Leukaemia Res Inst, 3D Chromatin Org Grp, Badalona 08916, Spain
Barcelona Supercomp Ctr BSC, Barcelona, Spain
Gusi-Vives, M:
Josep Carreras Leukaemia Res Inst, Lymphocyte Dev & Dis Grp, Badalona 08916, Spain
Graf, T:
Ctr Genom Regulat CRG, PRBB Bldg,Dr Aiguader 88, Barcelona 08003, Spain
Univ Pompeu Fabra, Barcelona, Spain
Varela, I:
Univ Cantabria, Inst Biomed & Biotecnol Cantabria, CSIC, Santander 39011, Spain
:
Josep Carreras Leukaemia Res Inst, Epigenet Control Haematopoiesis Grp, Badalona 08916, Spain
:
Josep Carreras Leukaemia Res Inst, 3D Chromatin Org Grp, Badalona 08916, Spain
:
Josep Carreras Leukaemia Res Inst, Lymphocyte Dev & Dis Grp, Badalona 08916, Spain
Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Cellular Differentiat Grp, Av Gran Via 199, Barcelona 08908, Spain
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