Producción CyT
Artículo
Autoría
Etchegaray, Jean Pierre
;
Chavez, Lukas
;
Huang, Yun
;
Ross, Kenneth N.
;
Choi, Jiho
;
Martinez Pastor, Barbara
;
Walsh, Ryan M.
;
Sommer, Cesar A.
;
Lienhard, Matthias
;
Gladden, Adrianne
;
Kugel, Sita
;
SILBERMAN, DAFNE MAGALI
;
Ramaswamy, Sridhar
;
Mostoslavsky, Gustavo
;
Hochedlinger, Konrad
;
Goren, Alon
;
Rao, Anjana
;
Mostoslavsky, Raul
Fecha
2015
Editorial y Lugar de Edición
Nature Publishing Group
Revista
NATURE CELL BIOLOGY.,
vol. 17
(pp. 545-557)
Nature Publishing Group
Resumen
Información suministrada por el agente en
SIGEVA
How embryonic stem cells (ESCs) commit to specific cell lineages and yield all cell types of a fully formed organism remains a major question. ESC differentiation is accompanied by large-scale histone and DNA modifications, but the relations between these epigenetic categories are not understood. Here we demonstrate the interplay between the histone deacetylase sirtuin 6 (SIRT6) and the ten-eleven translocation enzymes (TETs). SIRT6 targets acetylated histone H3 at Lys 9 and 56 (H3K9ac and H3K5...
How embryonic stem cells (ESCs) commit to specific cell lineages and yield all cell types of a fully formed organism remains a major question. ESC differentiation is accompanied by large-scale histone and DNA modifications, but the relations between these epigenetic categories are not understood. Here we demonstrate the interplay between the histone deacetylase sirtuin 6 (SIRT6) and the ten-eleven translocation enzymes (TETs). SIRT6 targets acetylated histone H3 at Lys 9 and 56 (H3K9ac and H3K56ac), while TETs convert 5-methylcytosine into 5-hydroxymethylcytosine (5hmC). ESCs derived from Sirt6 knockout (S6KO) mice are skewed towards neuroectoderm development. This phenotype involves derepression of OCT4, SOX2 and NANOG, which causes an upregulation of TET-dependent production of 5hmC. Genome-wide analysis revealed neural genes marked with 5hmC in S6KO ESCs, thereby implicating TET enzymes in the neuroectoderm-skewed differentiation phenotype. We demonstrate that SIRT6 functions as a chromatin regulator safeguarding the balance between pluripotency and differentiation through Tet-mediated production of 5hmC.
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Palabras Clave
DEVELOPMENTSTEM CELLSSITR6
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