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PXD008965

PXD008965 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleKMT9 writes the histone mark H4K12me1 and controls metabolism and proliferation of castration-resistant prostate cancer cells
DescriptionPosttranslational 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.
HostingRepositoryPRIDE
AnnounceDate2019-03-11
AnnouncementXMLSubmission_2019-03-11_04:35:08.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAndreas Schmidt
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonomethylated residue; acetylated residue; dimethylated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-02-15 09:26:18ID requested
12019-03-11 04:35:09announced
Publication List
Dataset with its publication pending
Keyword List
curator keyword: Biological, Biomedical
submitter keyword: Lysine methylation, methyltransferase, methyl-SILAC, chromatin, prostate cancer, H4K12me1, KMT9, TRMT112
Contact List
Axel Imhof
contact affiliationProtein Analysis Unit ZfP LMU Munich BioMedical Center Grosshaderner Strasse 9 82152 Planegg-Martinsried Tel. +49 89 2180 71804
contact emailimhof@lmu.de
lab head
Andreas Schmidt
contact affiliationAdolf-Butenandt-Institut
contact emailA.Schmidt@med.uni-muenchen.de
dataset submitter
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Dataset FTP location
PRIDE project URI
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