PXD028148

PXD028148 is an original dataset announced via ProteomeXchange.

Title	Study of ALKBH4 negatively regulating the expression level of DNMT1 by conducting a quantitative proteomic experiment to reveal the differential expression of proteins in HEK293T cells upon genetic ablation of ALKBH4
Description	ALKBH4 is a versatile demethylase that catalyzes the removal of methyl group from monomethylated lysine-84 on actin and N6-methyladenine in DNA. We conducted a quantitative proteomic experiment to reveal the differential expression of proteins in HEK293T cells upon genetic ablation of ALKBH4. Our results revealed markedly diminished levels of GSTP1 and HSPB1 proteins in ALKBH4-depleted cells, which emanate from an augmented expression level of DNA (cytosine-5)-methyltransferase 1 (DNMT1) and the ensuing elevated cytosine methylation in the promoter regions of GSTP1 and HSPB1 genes in ALKBH4-deficient cells. Together, our results revealed a role of ALKBH4 in modulating DNA cytosine methylation through regulating the expression level of DNMT1 protein. Yeast two-hybrid screening identified several proteins that are associated with chromatin and/or involved with transcription, as interaction partners of human ALKBH4, though global gene expression was only marginally changed upon overexpression of ALKBH4. We reason that a comprehensive assessment of how genetic depletion of ALKBH4 modulates protein expression at the global proteome scale may provide new insights into the biological function of ALKBH4 protein. In the present study, we conducted such an analysis and we found that CRISPR-mediated ablation of ALKBH4 led to substantial changes in expression of a large number of proteins, including the markedly diminished expression of GSTP1 and HSPB1 proteins. Mechanistically, these changes arise from elevated expression of DNMT1 and the ensuing epigenetic silencing of these two genes.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:30:46.717.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kailin Yu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-26 04:06:31	ID requested
1	2021-12-29 23:15:19	announced
⏵ 2	2024-10-22 05:30:47	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Human, LC-MS, HEK293T cells, SILAC labeling

Yinsheng Wang
contact affiliation	Wang lab, Department of Chemistry, University of Riverside,California, United States
contact email	yinsheng@ucr.edu
lab head
Kailin Yu
contact affiliation	Researcher
contact email	kailiny1992@163.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/12/PXD028148

PRIDE project URI

• PRIDE
  1. PXD028148
     1. Label: PRIDE project
     2. Name: Study of ALKBH4 negatively regulating the expression level of DNMT1 by conducting a quantitative proteomic experiment to reveal the differential expression of proteins in HEK293T cells upon genetic ablation of ALKBH4