Aire regulates chromatin looping by evicting CTCF from domain boundaries and favoring accumulation of cohesin on superenhancers Journal Article
| Authors: | Bansal, K.; Michelson, D. A.; Ramirez, R. N.; Viny, A. D.; Levine, R. L.; Benoist, C.; Mathis, D. |
| Article Title: | Aire regulates chromatin looping by evicting CTCF from domain boundaries and favoring accumulation of cohesin on superenhancers |
| Abstract: | Aire controls immunological tolerance by driving promiscuous expression of a large swath of the genome in medullary thymic epithelial cells (mTECs). Its molecular mechanism remains enigmatic. High-resolution chromosome-conformation capture (Hi-C) experiments on ex vivo mTECs revealed Aire to have a widespread impact on higher-order chromatin structure, disfavoring architectural loops while favoring transcriptional loops. In the presence of Aire, cohesin complexes concentrated on superenhancers together with mediator complexes, while the CCCTC-binding factor (CTCF) was relatively depleted from structural domain boundaries. In particular, Aire associated with the cohesin loader, NIPBL, strengthening this factor’s affiliation with cohesin’s enzymatic subunits. mTEC transcripts up-regulated in the presence of Aire corresponded closely to those down-regulated in the absence of one of the cohesin subunits, SA-2. A mechanistic model incorporating these findings explains many of the unusual features of Aire’s impact on mTEC transcription, providing molecular insight into tolerance induction. © 2021 National Academy of Sciences. All rights reserved. |
| Keywords: | controlled study; nonhuman; cohesin; animal cell; mouse; animal tissue; protein depletion; protein metabolism; animal experiment; immune tolerance; enzyme regulation; thymus; chromatin; transcription; epithelium cell; down regulation; upregulation; protein structure; enzyme subunit; transcription factor ctcf; male; article; looping; autoimmune regulator protein |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 118 |
| Issue: | 38 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2021-09-21 |
| Start Page: | e2110991118 |
| Language: | English |
| DOI: | 10.1073/pnas.2110991118 |
| PROVIDER: | scopus |
| PUBMED: | 34518235 |
| PMCID: | PMC8463806 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2021 -- Source: Scopus |
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