title: Lysine-specific demethylase 1 (LSD1) and histone deacetylase 1 (HDAC1) synergistically repress proinflammatory cytokines and classical complement pathway components.
abstract: Histone modifying enzymes confer epigenetic marks, directing the changes in gene expression required for diverse cellular processes. Lysine-specific demethylase 1 (LSD1) functions as a transcriptional coregulator by demethylating histone H3 on lysine 4 and lysine 9. Analyzing transcriptomes on microarrays, we identified genes which represent inflammatory-related targets of LSD1. We demonstrate a repressive role of LSD1 in proinflammatory cytokine expression such as IL1α, IL1β, IL6 and IL8 and classical complement components. Consistently, LSD1 occupies and regulates the promoter of these genes. In addition, we demonstrate that HDAC1 and LSD1 synergistically regulate these inflammatory-related genes. Our data reveal a novel role for LSD1 in suppressing immune responses.
authors.affiliation: Institute of Pathology, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Janzer
authors.forename: Soyoung
authors.initials: S
authors.lastname: Lim
authors.forename: Florian
authors.initials: F
authors.lastname: Fronhoffs
authors.forename: Naima
authors.initials: N
authors.lastname: Niazy
authors.forename: Reinhard
authors.initials: R
authors.lastname: Buettner
authors.forename: Jutta
authors.initials: J
authors.lastname: Kirfel
mesh_terms: D045744:Cell Line, Tumor; D003171:Complement Pathway, Classical / Q000235:genetics*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000235:genetics*; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007109:Immunity / Q000235:genetics*; D007249:Inflammation / Q000235:genetics*
chemical_list: D016207:Cytokines; D056466:Histone Demethylases; C495195:KDM1A protein, human; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1