PXD039708

PXD039708 is an original dataset announced via ProteomeXchange.

Title	dBRWD3 manipulates chromatin signature by ubiquitination to regulate ORC
Description	Ubiquitination and epigenetic modification both play essential roles in regulating cell fates and development, but little is known how two pathways crosstalk. A known chromatin-binding protein BRWD3, Bromodomain repeats and WD40 repeats domain contain protein 3, has been shown involved both in ubiquitination and histone modification regulation. BRWD3 has roles in multiple chromatin-related processes, including transcription, DNA replication, and chromatin modification. However, how ubiquitination is involved and what’s BRWD3’s ubiquitination targets are barely known. Here, we study the single Drosophila homolog dBRWD3 to uncover its mechanism. To find dBRWD3’s ubiquitination targets, we performed both dBRWD3 IP-MS and BRWD3 dependent ubiquitination IP-MS. Expectedly, the whole BRWD3-Cul4-DDB1 E3 ubiquitination complex and multiple histones are significantly enriched in dBRWD3-IP. Interestingly, multiple histone modification writers and the DNA replication initiation factor origin recognition complex (ORC) are among the intersection of two MS. ORC’s function is highly dependent on chromatin signature. dBRWD3 could provide a perspective on how chromatin signature is regulated by ubiquitination to regulate ORC function. In support of this, about 35% of ORC2 binding sites overlap with dBRWD3 binding sites among the genome. The H3K27ac occupancy rate of dBRWD3 related ORC sites is about 50% higher than that of dBRWD3 irrelevant ORC sites. Depletion of dBRWD3 significantly reduces DNA proliferation in the S phase. Further study will focus on determining which histone modification writer is targeted for ubiquitination and how does it contribute to the chromatin signature and ORC function.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:09:18.063.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jonathan Davies
SpeciesList	scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: 7227;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-27 10:50:52	ID requested
1	2023-10-24 11:51:26	announced
2	2023-11-14 09:08:38	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:09:20	announced	2024-10-22: Updated project metadata.

10.1073/pnas.2305092120;

Han D, Schaffner SH, Davies JP, Benton ML, Plate L, Nordman JT, BRWD3 promotes KDM5 degradation to maintain H3K4 methylation levels. Proc Natl Acad Sci U S A, 120(39):e2305092120(2023) [pubmed]

submitter keyword: histone, WD40, degradation, E3 ubiquitin ligase,dBRWD3, ORC

Jared Nordman
contact affiliation	Department of Biological Sciences, Vanderbilt University
contact email	jared.nordman@vanderbilt.edu
lab head
Jonathan Davies
contact affiliation	Vanderbilt University
contact email	jonathan.p.davies@vanderbilt.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD039708
     1. Label: PRIDE project
     2. Name: dBRWD3 manipulates chromatin signature by ubiquitination to regulate ORC