PXD003983

PXD003983 is an original dataset announced via ProteomeXchange.

Title	Hemi-methylated DNA regulates DNA methylation inheritance through allosteric control of H3 ubiquitylation by UHRF1
Description	DNA 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.
HostingRepository	PRIDE
AnnounceDate	2016-08-25
AnnouncementXML	Submission_2017-06-13_08:32:37.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dennis Goldfarb
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; ubiquitination signature dipeptidyl lysine; trimethylated residue; phosphorylated residue; monohydroxylated residue; acetylated residue; dimethylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2016-04-18 06:06:44	ID requested
1	2016-08-25 05:00:31	announced
⏵ 2	2017-06-13 08:32:38	announced	Updated publication reference for PubMed record(s): 27595565.

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]

curator keyword: Biological

submitter keyword: DNA methylation, epigenetics, histone post-translational modifications, ubiquitin, UHRF1, RING E3 ligase, histone H3 ubiquitylation

Scott Rothbart
contact affiliation	Center for Epigenetics Van Andel Research Institute Grand Rapics, Michigan 49503, USA
contact email	scott.rothbart@vai.org
lab head
Dennis Goldfarb
contact affiliation	Cell and Developmental Biology
contact email	dennisg@email.unc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD003983
     1. Label: PRIDE project
     2. Name: Hemi-methylated DNA regulates DNA methylation inheritance through allosteric control of H3 ubiquitylation by UHRF1