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KMT9 writes the H4K12me1 histone mark and controls metabolism and proliferation of castration-resistant prostate cancer cells [ChIP-seq]

ABSTRACT: KMT9 is formed by the assembly of KMT9a and KMT9b and writes the H4K12me1 mark. The objectives of this study is to identify KMT9a, KMT9b, and H4K12me1 locations by ChIP-seq in the androgen-independent PC-3M prostate cancer cells and to show that upon KMT9a knockdown the levels of H4K12me1 mark decrease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE117534 | GEO | 2019/06/26

REPOSITORIES: GEO

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KMT9a writes the H4K12me1 histone mark and controls metabolism and proliferation of castration-resistant prostate cancer cells [RNA-seq]

Project description:The aim of the RNA-seq was to identify the KMT9 transcriptome in PC-3M cells. The MCF10A breast epithelial cells that do not express KMT9a were used to show that the siRNA against KMT9 show no off-target effects.

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KMT9 writes the H4K12me1 histone mark and controls metabolism and proliferation of castration-resistant prostate cancer cells [ChIP-Seq 2]

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KMT9 writes the histone mark H4K12me1 and controls metabolism and proliferation of castration-resistant prostate cancer cells

Project 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.

2019-03-11 | PXD008965 | Pride

KMT9a writes the H4K12me1 histone mark and controls metabolism and proliferation of castration-resistant prostate cancer cells

Project description:This SuperSeries is composed of the SubSeries listed below. 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 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. We characterized the recognition mode of H4K12 by KMT9 that is formed by the assembly of KMT9a with KMT9b by solving the co-crystal structure. Genome-wide analyses revealed KMT9 and H4K12me1 enrichment at promoters of KMT9 target genes. By controlling expression of genes involved in cell cycle regulation, KMT9 regulates proliferation of 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 cell cycle 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.

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KMT9 writes the H4K12me1 histone mark and controls metabolism and proliferation of castration-resistant prostate cancer cells [ChIP-seq]

Project description:KMT9 writes the H4K12me1 histone mark and controls metabolism and proliferation of castration-resistant prostate cancer cells [ChIP-seq]

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KMT9 writes the H4K12me1 histone mark and controls metabolism and proliferation of castration-resistant prostate cancer cells [ChIP-Seq 2]

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