Nuclear Phosphoinositides Contribute to Organization of Transcription Sites and Regulation of Gene Expression

0473258 - ÚMG 2017 RIV DE eng C - Konferenční příspěvek (zahraniční konf.)
Hozák, Pavel - Philimonenko, Vlada - Sobol, Margaryta - Kalasová, Ilona
Nuclear Phosphoinositides Contribute to Organization of Transcription Sites and Regulation of Gene Expression.
Cytogenetic and Genome Research. Vol. 148. Würzburg: Karger, 2016. ISBN N. ISSN 1424-8581. E-ISSN 1424-859X.
[21st International Chromosome Conference (ICC). Foz do Iguaçu (BR), 10.07.2016-13.07.2016]
Grant CEP: GA ČR GA15-08738S; GA TA ČR(CZ) TE01020118; GA MŠMT(CZ) ED1.1.00/02.0109; GA ČR(CZ) GA16-03346S
Institucionální podpora: RVO:68378050
Klíčová slova: nucleus * PIP2 islets * transcription * microscopy
Kód oboru RIV: EB - Genetika a molekulární biologie

The nucleus is a highly organized cell compartment, where controlled gene expression, DNA replication, and RNA processing occur. These processes are spatially ordered via the nucleoskeleton, which is involved in nuclear compartmentalization and critical for nuclear functioning. In spite of the growing interest and extensive research concerned to the nuclear organization, so far mostly protein complexes have been found as important for spatial nuclear ordering. We describe here novel structures containing phosphatidylinositol 4,5-bisphosphate (PIP2) which contribute as well. Based on scarce literature data relating to PIP2 presence in interchromatin granule clusters and in the nucleolus, we carried out ultrastructural mapping of pip2-containing structures using pre-embedding immunolabelling and 3D electron tomography, EELS and super-resolution fluorescence microscopy together with molecular biology experiments. We identified previously undescribed nucleoplasmic structures decorated by PIP2 molecules, and demonstrated that these structures, referred to as PIP2 islets, are evolutionary conserved. They are surrounded by nucleic acids and protein-containing compounds. At the islet periphery, PIP2 co-localizes with nascent RNA transcripts and the proteins engaged in Pol II transcription and organization of chromatin. PIP2 islets are sensitive to RNase treatment, and their enzymatic disruption affects the level of transcription. Additional data on islets attached molecular complexes will be presented. Based on our findings, we suggest that PIP2 islets play an important role in the organization of nuclear architecture providing multiple stable surfaces for the formation of the RNA polymerase I/II transcription complexes. Taken together, this data allowed us to suggest for the first time that PIP2 as a lipid representative plays an important role in the organization of chromatin architecture and in regulation of gene transcription. The result will be discussed in the frame of the current nucleolar and transcription factories models, and lipid functions in the cell nucleus.
Trvalý link: http://hdl.handle.net/11104/0270470