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1篇 您的检索式:作者名="Arndt G.Benecke"
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1A TDG/CBP/RARα Ternary Complex Mediates the Retinoic Acid-dependent Expression of DNA Methylation-sensitive Genes显示文摘The thymine DNA glycosylase(TDG) is a multifunctional enzyme,which is essential for embryonic development.It mediates the base excision repair(BER) of G:T and G:U DNA mismatches arising from the deamination of 5-methyl cytosine(5-MeC) and cytosine,respectively.Recent studies have pointed at a role of TDG during the active demethylation of 5-MeC within CpG islands.TDG interacts with the histone acetylase CREB-binding protein(CBP) to activate CBP-dependent transcription.In addition,TDG also interacts with the retinoic acid receptor a(RARα),resulting in the activation of RARα target genes.Here we provide evidence for the existence of a functional ternary complex containing TDG,CBP and activated RARα.Using global transcriptome profiling,we uncover a coupling of de novo methylation-sensitive and RA-dependent transcription,which coincides with a significant subset of CBP target genes.The introduction of a point mutation in TDG,which neither affects overall protein structure nor BER activity,leads to a significant loss in ternary complex stability,resulting in the deregulation of RA targets involved in cellular networks associated with DNA replication,recombination and repair.We thus demonstrate for the first time a direct coupling of TDG's epigenomic and transcription regulatory function through ternary complexes with CBP and RARα.Hélène Léger Caroline Smet-Nocca Amel Attmane-Elakeb Sara Morley-Fletcher Arndt G.Benecke Sebastian Eilebrecht 2014Genomics, Proteomics & Bioinformatics2014,12,1:1
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