PXD008965-1

PXD008965 is an original dataset announced via ProteomeXchange.

Title	KMT9 writes the histone mark H4K12me1 and controls metabolism and proliferation of castration-resistant prostate cancer cells
Description	Posttranslational modifications of histones such as methylation regulate chromatin structure and gene expression. Methylation of histone lysine residues is generally performed by SET domain methyltransferases. Here, we identify the heterodimeric C21orf127/TRMT112 complex as a specific histone methyltransferase. Assembly of the seven-b-strand protein C21orf127 (also named Hemk2, N6amt1 or PrmC) with TRMT112 is essential to form an active enzyme, hereafter named KMT9 that writes the histone mark H4K12me1 in vitro and in vivo. The H4K12me1 mark is enriched at promoters of KMT9 target genes and co-localises with the active histone mark H4K12ac. By controlling expression of genes involved in energy metabolism, KMT9 regulates oxidative phosphorylation in androgen receptor-dependent and -independent prostate tumour cells. Importantly, KMT9 depletion severely affects proliferation of castration and enzalutamide-resistant prostate cancer cells and xenograft tumours. Together, our data link the writing of the H4K12me1 histone mark by KMT9 with KMT9-dependent gene expression, which in consequence regulates energy metabolism and proliferation. KMT9 executes these functions independently of androgen receptor and androgen signalling thus, providing a promising paradigm for the treatment of castration resistant prostate cancer.
HostingRepository	PRIDE
AnnounceDate	2019-03-11
AnnouncementXML	Submission_2019-03-11_04:35:08.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andreas Schmidt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; acetylated residue; dimethylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-02-15 09:26:18	ID requested
⏵ 1	2019-03-11 04:35:09	announced

Dataset with its publication pending

curator keyword: Biological, Biomedical

submitter keyword: Lysine methylation, methyltransferase, methyl-SILAC, chromatin, prostate cancer, H4K12me1, KMT9, TRMT112

Axel Imhof
contact affiliation	Protein Analysis Unit ZfP LMU Munich BioMedical Center Grosshaderner Strasse 9 82152 Planegg-Martinsried Tel. +49 89 2180 71804
contact email	imhof@lmu.de
lab head
Andreas Schmidt
contact affiliation	Adolf-Butenandt-Institut
contact email	A.Schmidt@med.uni-muenchen.de
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/2019/03/PXD008965

PRIDE project URI

• PRIDE
  1. PXD008965
     1. Label: PRIDE project
     2. Name: KMT9 writes the histone mark H4K12me1 and controls metabolism and proliferation of castration-resistant prostate cancer cells