PXD006476

PXD006476 is an original dataset announced via ProteomeXchange.

Title	S-adenosylhomocysteine hydrolase participates in DNA methylation inheritance
Description	DNA (cytosine-5) methyltransferase 1 (DNMT1) is essential for mammalian development and maintenance of DNA methylation following DNA replication in cells. The DNA methylation process generates S-adenosyl-L-homocysteine, a strong inhibitor of DNMT1. Here we report that S-adenosylhomocysteine hydrolase (SAHH/AHCY), the only mammalian enzyme capable of hydrolyzing S-adenosyl-L-homocysteine binds to DNMT1 during DNA replication. SAHH activates DNMT1 in vitro and its overexpression in mammalian cells leads to hypermethylation of the genome, whereas its inhibition by adenosine periodate resulted in hypomethylation of the genome. Hypermethylation was consistent in both gene bodies and repetitive DNA elements leading to both down- and up-regulation of genes. Similarly, hypomethylation led to both up- and down-regulation of genes suggesting methylated regions influence gene expression either positively or negatively. Cells overexpressing SAHH specifically up-regulated metabolic pathway genes and down-regulated PPAR and MAPK signaling pathways genes. Therefore, we suggest that alteration of SAHH level in the cell leads to aberrant DNA methylation, altered metabolite levels and gene expression.
HostingRepository	PRIDE
AnnounceDate	2018-06-06
AnnouncementXML	Submission_2018-06-06_06:22:49.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	V K Chaithanya Ponnaluri
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	2017-05-09 23:50:16	ID requested
⏵ 1	2018-06-06 06:22:50	announced

Ponnaluri VKC, Est, è, ve PO, Ruse CI, Pradhan S, S-adenosylhomocysteine Hydrolase Participates in DNA Methylation Inheritance. J Mol Biol, 430(14):2051-2065(2018) [pubmed]

curator keyword: Biological

submitter keyword: DNMT1, SAHH, Cell cycle

Sriharsa Pradhan
contact affiliation	New England Biolabs Inc.
contact email	pradhan@neb.com
lab head
V K Chaithanya Ponnaluri
contact affiliation	New England Biolabs
contact email	ponnaluri@neb.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/2018/06/PXD006476

PRIDE project URI

• PRIDE
  1. PXD006476
     1. Label: PRIDE project
     2. Name: S-adenosylhomocysteine hydrolase participates in DNA methylation inheritance