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oai:repisalud.isciii.es:20.500.12105/262172025-12-18T12:54:25Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Etchegaray, Jean-Pierre author Chavez, Lukas author Huang, Yun author Ross, Kenneth N author Choi, Jiho author Martinez-Pastor, Barbara author Walsh, Ryan M author Sommer, Cesar A author Lienhard, Matthias author Gladden, Adrianne author Kugel, Sita author Silberman, Dafne M author Ramaswamy, Sridhar author Mostoslavsky, Gustavo author Hochedlinger, Konrad author Goren, Alon author Rao, Anjana author Mostoslavsky, Raul author 2015-05 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. https://pmc.ncbi.nlm.nih.gov/articles/PMC4593707/pdf/nihms725229.pdf 25915124 https://hdl.handle.net/20.500.12105/26217 The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine.