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Transcription induces context-dependent remodeling of chromatin architecture during differentiation.

Sanjay Chahar, Yousra Ben Zouari, Hossein Salari, Dominique Kobi, Manon Maroquenne, Cathie Erb, Anne M Molitor, Audrey Mossler, Nezih Karasu, Daniel Jost, and Tom Sexton (2023)

PLoS Biol, 21(12):e3002424.

Metazoan chromosomes are organized into discrete spatial domains (TADs), believedto contribute to the regulation of transcriptional programs. Despite extensivecorrelation between domain organization and gene activity, a direct mechanisticlink is unclear, with perturbation studies often showing little effect. To followchromatin architecture changes during development, we used Capture Hi-C tointerrogate the domains around key differentially expressed genes during mousethymocyte maturation, uncovering specific remodeling events. Notably, one TADboundary was broadened to accommodate RNA polymerase elongation past the border,and subdomains were formed around some activated genes without changes in CTCFbinding. The ectopic induction of some genes was sufficient to recapitulatedomain formation in embryonic stem cells, providing strong evidence thattranscription can directly remodel chromatin structure. These results suggestthat transcriptional processes drive complex chromosome folding patterns that canbe important in certain genomic contexts.

 
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