title: Epigenetic gene regulation by histone demethylases: emerging role in oncogenesis and inflammation.
abstract: Histone N-terminal tails of nucleosomes are the sites of complex regulation of gene expression through post-translational modifications. Among these modifications, histone methylation had long been associated with permanent gene inactivation until the discovery of Lys-specific demethylase (LSD1), which is responsible for dynamic gene regulation. There are more than 30 members of the Lys demethylase (KDM) family, and with exception of LSD1 and LSD2, all other KDMs possess the Jumonji C (JmjC) domain exhibiting demethylase activity and require unique cofactors, for example, Fe(II) and α-ketoglutarate. These cofactors have been targeted when devising KDM inhibitors, which may yield therapeutic benefit. KDMs and their counterpart Lys methyltransferases (KMTs) regulate multiple biological processes, including oncogenesis and inflammation. KDMs' functional interactions with retinoblastoma (Rb) and E2 factor (E2F) target promoters illustrate their regulatory role in cell cycle progression and oncogenesis. Recent findings also demonstrate the control of inflammation and immune functions by KDMs, such as KDM6B that regulates the pro-inflammatory gene expression and CD4+T helper (Th) cell lineage determination. This review will highlight the mechanisms by which KDMs and KMTs regulate the target gene expression and how epigenetic mechanisms may be applied to our understanding of oral inflammation.
authors: Shapiro Laboratory of Viral Oncology and Aging Research, Los Angeles, CA, USA.
authors: M K
authors: MK
authors: Kang
authors: Shapiro Laboratory of Viral Oncology and Aging Research, Los Angeles, CA, USA.
authors: S
authors: S
authors: Mehrazarin
authors: Shapiro Laboratory of Viral Oncology and Aging Research, Los Angeles, CA, USA.|David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
authors: N-H
authors: NH
authors: Park
authors: Laboratory of Molecular Signaling, UCLA School of Dentistry, Los Angeles, CA, USA.
authors: C-Y
authors: CY
authors: Wang
mesh_terms: D000539:Alveolar Process / Q000254:growth & development; D063646:Carcinogenesis / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics*; D055113:Chronic Periodontitis / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D056466:Histone Demethylases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D014070:Tooth / Q000254:growth & development
chemical_list: D056466:Histone Demethylases
keywords: epigenetics; histone lysine methylation; oncogenesis; oral inflammation