Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 67,113 bioRxiv papers from 295,324 authors.
Pericentromeric hypomethylation elicits an interferon response in an animal model of ICF syndrome
Paige K Arnold,
Sara G Payne,
Teresa V Bowman,
Robert J Schmitz,
John R Edwards,
Mary G Goll
Posted 23 Aug 2018
bioRxiv DOI: 10.1101/396671 (published DOI: 10.7554/elife.39658)
Posted 23 Aug 2018
Pericentromeric satellite repeats are enriched in 5-methylcytosine (5mC). Loss of 5mC at these sequences is common in cancer and is a hallmark of Immunodeficiency, Centromere and Facial abnormalities (ICF) syndrome. While the general importance of 5mC is well-established, the specific functions of 5mC at pericentromeres are less clear. To address this deficiency, we generated a viable animal model of pericentromeric hypomethylation through mutation of the ICF-gene ZBTB24. Deletion of zebrafish zbtb24 caused a progressive loss of 5mC at pericentromeres and ICF-like phenotypes. Hypomethylation of these repeats triggered derepression of pericentromeric transcripts and activation of an interferon-based innate immune response. Injection of pericentromeric RNA is sufficient to elicit this response in wild-type embryos, and mutation of the MDA5-MAVS dsRNA-sensing machinery blocks the response in mutants. These findings identify activation of the innate immune system as an early consequence of pericentromeric hypomethylation, implicating derepression of pericentromeric transcripts as a trigger of autoimmunity.
- Downloaded 501 times
- Download rankings, all-time:
- Site-wide: 20,974 out of 67,118
- In molecular biology: 606 out of 2,139
- Year to date:
- Site-wide: 15,053 out of 67,118
- Since beginning of last month:
- Site-wide: 15,672 out of 67,118
Downloads over time
Distribution of downloads per paper, site-wide
- Top preprints of 2018
- Paper search
- Author leaderboards
- Overall metrics
- The API
- Email newsletter
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!