Nucleic acids research, 2017-01, Vol.45 (1), p.92
2017
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Details
- Autor(en) / Beteiligte
- Titel
- SPOP-containing complex regulates SETD2 stability and H3K36me3-coupled alternative splicing
- Ist Teil von
- Nucleic acids research, 2017-01, Vol.45 (1), p.92
- Ort / Verlag
- England
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Trimethylation of histone H3K36 is a chromatin mark associated with active gene expression, which has been implicated in coupling transcription with mRNA splicing and DNA damage response. SETD2 is a major H3K36 trimethyltransferase, which has been implicated as a tumor suppressor in mammals. Here, we report the regulation of SETD2 protein stability by the proteasome system, and the identification of SPOP, a key subunit of the CUL3 ubiquitin E3 ligase complex, as a SETD2-interacting protein. We demonstrate that SPOP is critically involved in SETD2 stability control and that the SPOP/CUL3 complex is responsible for SETD2 polyubiquitination both in vivo and in vitro ChIP-Seq analysis and biochemical experiments demonstrate that modulation of SPOP expression confers differential H3K36me3 on SETD2 target genes, and induce H3K36me3-coupled alternative splicing events. Together, these findings establish a functional connection between oncogenic SPOP and tumor suppressive SETD2 in the dynamic regulation of gene expression on chromatin.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1362-4962DOI: 10.1093/nar/gkw814Titel-ID: cdi_pubmed_primary_27614073
- Format
- –
- Schlagworte
- Alternative Splicing, Cell Line, Tumor, Cloning, Molecular, Escherichia coli - genetics, Escherichia coli - metabolism, Gene Expression, HEK293 Cells, Histone-Lysine N-Methyltransferase - genetics, Histone-Lysine N-Methyltransferase - metabolism, Histones - genetics, Histones - metabolism, Humans, Methylation, Neoplastic Stem Cells, Nuclear Proteins - genetics, Nuclear Proteins - metabolism, Proteasome Endopeptidase Complex - metabolism, Protein Binding, Protein Isoforms - genetics, Protein Isoforms - metabolism, Protein Stability, Recombinant Proteins - genetics, Recombinant Proteins - metabolism, Repressor Proteins - genetics, Repressor Proteins - metabolism, Signal Transduction, Ubiquitination