التفاصيل البيبلوغرافية
| العنوان: |
UHRF1 ubiquitin ligase activity supports the maintenance of low-density CpG methylation. |
| المؤلفون: |
Tiedemann RL, Hrit J, Du Q, Wiseman AK, Eden HE, Dickson BM, Kong X, Chomiak AA, Vaughan RM, Hebert JM, David Y, Zhou W, Baylin SB, Jones PA, Clark SJ, Rothbart SB |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Feb 16. Date of Electronic Publication: 2024 Feb 16. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
The RING E3 ubiquitin ligase UHRF1 is an established cofactor for DNA methylation inheritance. Nucleosomal engagement through histone and DNA interactions directs UHRF1 ubiquitin ligase activity toward lysines on histone H3 tails, creating binding sites for DNMT1 through ubiquitin interacting motifs (UIM1 and UIM2). Here, we profile contributions of UHRF1 and DNMT1 to genome-wide DNA methylation inheritance and dissect specific roles for ubiquitin signaling in this process. We reveal DNA methylation maintenance at low-density CpGs is vulnerable to disruption of UHRF1 ubiquitin ligase activity and DNMT1 ubiquitin reading activity through UIM1. Hypomethylation of low-density CpGs in this manner induces formation of partially methylated domains (PMD), a methylation signature observed across human cancers. Furthermore, disrupting DNMT1 UIM2 function abolishes DNA methylation maintenance. Collectively, we show DNMT1-dependent DNA methylation inheritance is a ubiquitin-regulated process and suggest a disrupted UHRF1-DNMT1 ubiquitin signaling axis contributes to the development of PMDs in human cancers. |
| معلومات مُعتمدة: |
R35 GM138386 United States GM NIGMS NIH HHS |
| تواريخ الأحداث: |
Date Created: 20240226 Latest Revision: 20240308 |
| رمز التحديث: |
20240308 |
| مُعرف محوري في PubMed: |
PMC10888769 |
| DOI: |
10.1101/2024.02.13.580169 |
| PMID: |
38405904 |
| قاعدة البيانات: |
MEDLINE |
