CTCF mediates dosage- and sequence-context-dependent transcriptional insulation by forming local chromatin domains View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2021-05-17

AUTHORS

Hui Huang, Quan Zhu, Adam Jussila, Yuanyuan Han, Bogdan Bintu, Colin Kern, Mattia Conte, Yanxiao Zhang, Simona Bianco, Andrea M. Chiariello, Miao Yu, Rong Hu, Melodi Tastemel, Ivan Juric, Ming Hu, Mario Nicodemi, Xiaowei Zhuang, Bing Ren

ABSTRACT

Insulators play a critical role in spatiotemporal gene regulation in animals. The evolutionarily conserved CCCTC-binding factor (CTCF) is required for insulator function in mammals, but not all of its binding sites act as insulators. Here we explore the sequence requirements of CTCF-mediated transcriptional insulation using a sensitive insulator reporter in mouse embryonic stem cells. We find that insulation potency depends on the number of CTCF-binding sites in tandem. Furthermore, CTCF-mediated insulation is dependent on upstream flanking sequences at its binding sites. CTCF-binding sites at topologically associating domain boundaries are more likely to function as insulators than those outside topologically associating domain boundaries, independently of binding strength. We demonstrate that insulators form local chromatin domain boundaries and weaken enhancer–promoter contacts. Taken together, our results provide genetic, molecular and structural evidence connecting chromatin topology to the action of insulators in the mammalian genome. More... »

PAGES

1064-1074

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    7

    VOLUME

    53

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-021-00863-6

    DOI

    http://dx.doi.org/10.1038/s41588-021-00863-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1138105592

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34002095


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