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The Sequence-Specific Transcription Factor c-Jun Targets Cockayne Syndrome Protein B to Regulate Transcription and Chromatin Structure


Cockayne syndrome is a devastating inherited disease, in which patients appear to age prematurely, have sun sensitivity and suffer from profound neurological and developmental defects. Mutations in the CSB gene account for the majority of Cockayne syndrome cases. CSB is an ATP-dependent chromatin remodeler, and these proteins can use energy from ATP-hydrolysis to alter contacts between DNA and histones of a nucleosome, the basic units of chromatin structure. CSB functions in DNA repair, but accumulating evidence reveals that CSB also functions in transcription regulation. Here, we determined the genomic localization of CSB to identify its gene targets and found that CSB occupancy displays high correlation to regions with epigenetic features of promoters and enhancers. Furthermore, CSB is enriched at genomic regions containing the binding site for the c-Jun transcription factor, and we found that these two proteins interact, uncovering a new targeting mechanism for CSB. We also demonstrate that CSB can influence gene expression in the vicinity of its binding sites and alter local chromatin structure. Together, this study supports the hypothesis that defects in the regulation of gene expression and chromatin structure by CSB might contribute to the diverse clinical features of Cockayne syndrome.


Vyšlo v časopise: The Sequence-Specific Transcription Factor c-Jun Targets Cockayne Syndrome Protein B to Regulate Transcription and Chromatin Structure. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004284
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004284

Souhrn

Cockayne syndrome is a devastating inherited disease, in which patients appear to age prematurely, have sun sensitivity and suffer from profound neurological and developmental defects. Mutations in the CSB gene account for the majority of Cockayne syndrome cases. CSB is an ATP-dependent chromatin remodeler, and these proteins can use energy from ATP-hydrolysis to alter contacts between DNA and histones of a nucleosome, the basic units of chromatin structure. CSB functions in DNA repair, but accumulating evidence reveals that CSB also functions in transcription regulation. Here, we determined the genomic localization of CSB to identify its gene targets and found that CSB occupancy displays high correlation to regions with epigenetic features of promoters and enhancers. Furthermore, CSB is enriched at genomic regions containing the binding site for the c-Jun transcription factor, and we found that these two proteins interact, uncovering a new targeting mechanism for CSB. We also demonstrate that CSB can influence gene expression in the vicinity of its binding sites and alter local chromatin structure. Together, this study supports the hypothesis that defects in the regulation of gene expression and chromatin structure by CSB might contribute to the diverse clinical features of Cockayne syndrome.


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