PIP2 epigenetically represses rRNA genes transcription interacting with PHF8
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
29246768
DOI
10.1016/j.bbalip.2017.12.008
PII: S1388-1981(17)30245-7
Knihovny.cz E-resources
- Keywords
- H3K9me2, Nucleus, PHF8, PIP2, rDNA transcription,
- MeSH
- Epigenesis, Genetic * MeSH
- Phosphatidylinositol 4,5-Diphosphate genetics metabolism MeSH
- Transcription, Genetic * MeSH
- Genes, rRNA * MeSH
- HEK293 Cells MeSH
- HeLa Cells MeSH
- Histone Demethylases genetics metabolism MeSH
- Humans MeSH
- Mutation MeSH
- Promoter Regions, Genetic * MeSH
- RNA, Ribosomal biosynthesis genetics MeSH
- Transcription Factors genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Phosphatidylinositol 4,5-Diphosphate MeSH
- Histone Demethylases MeSH
- PHF8 protein, human MeSH Browser
- RNA, Ribosomal MeSH
- Transcription Factors MeSH
Phosphoinositides are present in the plasma membrane, cytoplasm and inside the cell nucleus. Here we identify phosphatidylinositol-4,5-bisphosphate (PIP2) as a regulator of rRNA genes transcription at the epigenetic level. We show that PIP2 directly interacts with histone lysine demethylase PHF8 (PHD finger protein 8) and represses demethylation of H3K9me2 through this interaction. We identify the C-terminal K/R-rich motif as PIP2-binding site within PHF8, and address the function of this PIP2-PHF8 complex. PIP2-binding mutant of PHF8 has increased the activity of rDNA promoter (20%) and expression of pre-rRNA genes (47S-100%; 45S-66%). Furthermore, trypsin digestion reveals a potential conformational change of PHF8 upon PIP2 binding. These observations identify the function of nuclear PIP2, and suggest that PIP2 contributes to the fine-tuning of rDNA transcription.
References provided by Crossref.org
Lamin A/C and PI(4,5)P2-A Novel Complex in the Cell Nucleus
Super-Resolution Localisation of Nuclear PI(4)P and Identification of Its Interacting Proteome
Nuclear Phosphoinositides-Versatile Regulators of Genome Functions
Multiple Aspects of PIP2 Involvement in C. elegans Gametogenesis
Phospholipids and inositol phosphates linked to the epigenome
