PIP2 epigenetically represses rRNA genes transcription interacting with PHF8

0487322 - ÚMG 2018 RIV NL eng J - Journal Article
Uličná, Lívia - Kalendová, Alžběta - Kalasová, Ilona - Vacík, Tomáš - Hozák, Pavel
PIP2 epigenetically represses rRNA genes transcription interacting with PHF8.
Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids. Roč. 1863, č. 3 (2018), s. 266-275. ISSN 1388-1981. E-ISSN 1879-2618
R&D Projects: GA ČR GA15-08738S; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT(CZ) LM2015062
Institutional support: RVO:68378050
Keywords : PIP2 * PHF8 * rDNA transcription * H3K9me2 * Nucleus
OECD category: Biochemistry and molecular biology
Impact factor: 4.402, year: 2018

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.
Permanent Link: http://hdl.handle.net/11104/0281970