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PXD003983 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHemi-methylated DNA regulates DNA methylation inheritance through allosteric control of H3 ubiquitylation by UHRF1
DescriptionDNA methylation is a heritable chromatin modification essential to mammalian development that functions with histone post-translational modifications to regulate chromatin structure and gene expression programs. The epigenetic inheritance of DNA methylation requires the combined actions of DNMT1 and UHRF1, a histone- and DNA-binding RING E3 ubiquitin ligase that facilitates DNMT1 recruitment to sites of newly replicated DNA through the ubiquitylation of histone H3. UHRF1 binds DNA with modest selectivity towards hemi-methylated CpG dinucleotides (HeDNA); however, the contribution of HeDNA sensing to UHRF1 function remains elusive. Here, we reveal that the interaction of UHRF1 with HeDNA is required for DNA methylation inheritance but is dispensable for chromatin interaction, which is governed by reciprocal positive cooperativity between the UHRF1 histone- and DNA-binding domains. We further show that HeDNA functions as an allosteric regulator of UHRF1 ubiquitin ligase activity, directing ubiquitylation towards multiple lysines on the H3 tail adjacent to the UHRF1 histone-binding site. Collectively, our studies define a highly orchestrated epigenetic control mechanism involving modifications both to histones and DNA that facilitate UHRF1 chromatin targeting, H3 ubiquitylation, and DNA methylation inheritance.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDennis Goldfarb
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonomethylated residue; ubiquitination signature dipeptidyl lysine; trimethylated residue; phosphorylated residue; monohydroxylated residue; acetylated residue; dimethylated residue
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02016-04-18 06:06:44ID requested
12016-08-25 05:00:31announced
22017-06-13 08:32:38announcedUpdated publication reference for PubMed record(s): 27595565.
Publication List
Harrison JS, Cornett EM, Goldfarb D, DaRosa PA, Li ZM, Yan F, Dickson BM, Guo AH, Cantu DV, Kaustov L, Brown PJ, Arrowsmith CH, Erie DA, Major MB, Klevit RE, Krajewski K, Kuhlman B, Strahl BD, Rothbart SB, Hemi-methylated DNA regulates DNA methylation inheritance through allosteric activation of H3 ubiquitylation by UHRF1. Elife, 5():(2016) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: DNA methylation, epigenetics, histone post-translational modifications, ubiquitin, UHRF1, RING E3 ligase, histone H3 ubiquitylation
Contact List
Scott Rothbart
contact affiliationCenter for Epigenetics Van Andel Research Institute Grand Rapics, Michigan 49503, USA
contact emailscott.rothbart@vai.org
lab head
Dennis Goldfarb
contact affiliationCell and Developmental Biology
contact emaildennisg@email.unc.edu
dataset submitter
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Dataset FTP location
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