title: Chromatin associated SETD3 negatively regulates VEGF expression.
abstract: SETD3 is a member of the protein lysine methyltransferase (PKMT) family, which catalyzes the addition of methyl group to lysine residues. Accumulating data suggest that PKMTs are involved in the regulation of a broad spectrum of biological processes by targeting histone and non-histone proteins. Using a proteomic approach, we have identified 172 new SETD3 interacting proteins. We show that SETD3 binds and methylates the transcription factor FoxM1, which has been previously shown to be associated with the regulation of VEGF expression. We further demonstrate that under hypoxic conditions SETD3 is down-regulated. Mechanistically, we find that under basal conditions, SETD3 and FoxM1 are enriched on the VEGF promoter. Dissociation of both SETD3 and FoxM1 from the VEGF promoter under hypoxia correlates with elevated expression of VEGF. Taken together, our data reveal a new SETD3-dependent methylation-based signaling pathway at chromatin that regulates VEGF expression under normoxic and hypoxic conditions.
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, P.O.B. 653, Be'er-Sheva 84105, Israel.|National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, P.O.B. 653, Be'er-Sheva 84105, Israel.
authors.forename: Ofir
authors.initials: O
authors.lastname: Cohn
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, P.O.B. 653, Be'er-Sheva 84105, Israel.|National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, P.O.B. 653, Be'er-Sheva 84105, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Feldman
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, P.O.B. 653, Be'er-Sheva 84105, Israel.|National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, P.O.B. 653, Be'er-Sheva 84105, Israel.
authors.forename: Lital
authors.initials: L
authors.lastname: Weil
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, P.O.B. 653, Be'er-Sheva 84105, Israel.|National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, P.O.B. 653, Be'er-Sheva 84105, Israel.
authors.forename: Margarita
authors.initials: M
authors.lastname: Kublanovsky
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, P.O.B. 653, Be'er-Sheva 84105, Israel.|National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, P.O.B. 653, Be'er-Sheva 84105, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Levy
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D000072278:Forkhead Box Protein M1 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D002843:Chromatin; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C584641:SETD3 protein, human