Sin3a–Tet1 interaction activates gene transcription and is required for embryonic stem cell pluripotency

Citations Over TimeTop 10% of 2018 papers

Abstract

Sin3a is a core component of histone-deacetylation-activity-associated transcriptional repressor complex, playing important roles in early embryo development. Here, we reported that down-regulation of Sin3a led to the loss of embryonic stem cell (ESC) self-renewal and skewed differentiation into mesendoderm lineage. We found that Sin3a functioned as a transcriptional coactivator of the critical Nodal antagonist Lefty1 through interacting with Tet1 to de-methylate the Lefty1 promoter. Further studies showed that two amino acid residues (Phe147, Phe182) in the PAH1 domain of Sin3a are essential for Sin3a-Tet1 interaction and its activity in regulating pluripotency. Furthermore, genome-wide analyses of Sin3a, Tet1 and Pol II ChIP-seq and of 5mC MeDIP-seq revealed that Sin3a acted with Tet1 to facilitate the transcription of a set of their co-target genes. These results link Sin3a to epigenetic DNA modifications in transcriptional activation and have implications for understanding mechanisms underlying versatile functions of Sin3a in mouse ESCs.

Related Papers

• → How mammalian transcriptional repressors work(2004)111 cited
• → Reconstructing repressor protein levels from expression of gene targets in Escherichia coli(2006)28 cited
• → Dynamic equilibrium on DNA defines transcriptional regulation of a multidrug binding transcriptional repressor, LmrR(2017)9 cited
• → A Novel Transcriptional Repressor, Rhit, Is Involved in Heat-Inducible and Age-Dependent Expression of Mpv17-Like Protein, a Participant in Reactive Oxygen Species Metabolism(2010)7 cited
• → MAFG Is a Transcriptional Repressor of Bile Acid Synthesis and Metabolism(2016)