Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology; RNA Therapeutics Institute
Genomics | Structural Biology
Cohesin-mediated loop extrusion folds interphase chromosomes at the ten to hundreds kilobases scale. This process produces structural features such as loops and topologically associating domains. We identify three types of cis-elements that define the chromatin folding landscape generated by loop extrusion. First, CTCF sites form boundaries by stalling extruding cohesin, as shown before. Second, transcription termination sites form boundaries by acting as cohesin unloading sites. RNA polymerase II contributes to boundary formation at transcription termination sites. Third, transcription start sites form boundaries that are mostly independent of cohesin, but are sites where cohesin can pause. Together with cohesin loading at enhancers, and possibly other cis-elements, these loci create a dynamic pattern of cohesin traffic along the genome that guides enhancer-promoter interactions. Disturbing this traffic pattern, by removing CTCF barriers, renders cells sensitive to knock-out of genes involved in transcription initiation, such as the SAGA and TFIID complexes, and RNA processing such DEAD-Box RNA helicases. In the absence of CTCF, several of these factors fail to be efficiently recruited to active promoters. We propose that the complex pattern of cohesin movement along chromatin contributes to appropriate promoter-enhancer interactions and localization of transcription and RNA processing factors to active genes.
Genomics, chromatin, gene regulation, cohesin
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DOI of Published Version
bioRxiv 2021.07.29.454218; doi: https://doi.org/10.1101/2021.07.29.454218. Link to preprint on bioRxiv.
Valton A, Venev SV, Mair B, Khokhar E, Tong AH, Usaj M, Chan KS, Pai AA, Moffat J, Dekker J. (2021). A cohesin traffic pattern genetically linked to gene regulation [preprint]. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2021.07.29.454218. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/2081
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