Lysine-specific demethylase 1 (LSD1) and histone deacetylase 1 (HDAC1) synergistically repress proinflammatory cytokines and classical complement pathway components

被引:26
|
作者
Janzer, Andreas [1 ]
Lim, Soyoung [2 ]
Fronhoffs, Florian [1 ]
Niazy, Naima [1 ]
Buettner, Reinhard [2 ]
Kirfel, Jutta [1 ]
机构
[1] Univ Bonn, Inst Pathol, D-53127 Bonn, Germany
[2] Univ Cologne, Inst Pathol, D-50924 Cologne, Germany
关键词
Histone demethylases; LSD1; HDAC; Transcription; Inflammation; NECROSIS-FACTOR-ALPHA; CHROMATIN MODIFICATIONS; EPIGENETIC REGULATION; GENE-EXPRESSION; METHYLATION; INFLAMMATION; H3; CANCER; CELLS; PHOSPHORYLATION;
D O I
10.1016/j.bbrc.2012.04.057
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 IL1 alpha, IL1 beta, 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. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:665 / 670
页数:6
相关论文
共 50 条
  • [31] Fluorinated tranylcypromine analogues as inhibitors of lysine-specific demethylase 1 (LSD1, KDM1A)
    Borrello, Maria Teresa
    Schinor, Benjamin
    Bartels, Katharina
    Benelkebir, Hanae
    Pereira, Sara
    Al-Jamal, Wafa T.
    Douglas, Leon
    Duriez, Patrick J.
    Packham, Graham
    Haufe, Guenter
    Ganesan, A.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (10) : 2099 - 2101
  • [32] Crosstalk between lysine-specific demethylase 1 (LSD1) and histone deacetylases mediates antineoplastic efficacy of HDAC inhibitors in human breast cancer cells
    Vasilatos, Shauna N.
    Katz, Tiffany A.
    Oesterreich, Steffi
    Wan, Yong
    Davidson, Nancy E.
    Huang, Yi
    CARCINOGENESIS, 2013, 34 (06) : 1196 - 1207
  • [33] Lysine-Specific Demethylase 1 (LSD1) Inhibitors as Potential Treatment for Different Types of Cancers
    Abdel-Magid, Ahmed F.
    ACS MEDICINAL CHEMISTRY LETTERS, 2017, 8 (11): : 1134 - 1135
  • [34] Histone lysine demethylase LSD1 is required for adipogenesis
    Parrizas, M.
    Musri, M. M.
    Gomis, R.
    DIABETOLOGIA, 2009, 52 : S250 - S251
  • [35] Lysine-Specific Demethylase 1 (LSD1/KDM1A) Inhibition as a Target for Disease Modification in Myelofibrosis
    Gill, Harinder
    CELLS, 2022, 11 (13)
  • [36] Phosphorylation of neuronal Lysine-Specific Demethylase 1LSD1/KDM1A impairs transcriptional repression by regulating interaction with CoREST and histone deacetylases HDAC1/2
    Toffolo, Emanuela
    Rusconi, Francesco
    Paganini, Leda
    Tortorici, Marcello
    Pilotto, Simona
    Heise, Christopher
    Verpelli, Chiara
    Tedeschi, Gabriella
    Maffioli, Elisa
    Sala, Carlo
    Mattevi, Andrea
    Battaglioli, Elena
    JOURNAL OF NEUROCHEMISTRY, 2014, 128 (05) : 603 - 616
  • [37] Cervical Cancer: "Lysine-specific Histone Demethylase 1A" (LSD1) and "Nuclear Receptor Corepressor" (NCoR) as prognostic Factors
    Beilner, D.
    Kuhnc, C.
    Kost, B. P.
    Mahner, S.
    Schmoekel, E.
    Dannecker, C.
    Jeschke, U.
    Heidegger, H. H.
    GEBURTSHILFE UND FRAUENHEILKUNDE, 2020, 80 (10) : E185 - E185
  • [38] Discovery of a Novel Inhibitor of Histone Lysine-Specific Demethylase 1A (KDM1A/LSD1) as Orally Active Antitumor Agent
    Vianello, Paola
    Botrugno, Oronza A.
    Cappa, Anna
    Dal Zuffo, Roberto
    Dessanti, Paola
    Mai, Antonello
    Marrocco, Biagina
    Mattevi, Andrea
    Meroni, Giuseppe
    Minucci, Saverio
    Stazi, Giulia
    Thaler, Florian
    Trifiro, Paolo
    Valente, Sergio
    Villa, Manuela
    Varasi, Mario
    Mercurio, Ciro
    JOURNAL OF MEDICINAL CHEMISTRY, 2016, 59 (04) : 1501 - 1517
  • [39] Reversible Lysine Specific Demethylase 1 (LSD1) Inhibitors: A Promising Wrench to Impair LSD1
    Dai, Xing-Jie
    Liu, Ying
    Xue, Lei-Peng
    Xiong, Xiao-Peng
    Zhou, Ying
    Zheng, Yi-Chao
    Liu, Hong-Min
    JOURNAL OF MEDICINAL CHEMISTRY, 2021, 64 (05) : 2466 - 2488
  • [40] Impact Of Ovariectomy On Aldosterone And Blood Pressure In Lysine-Specific Demethylase 1 (LSD1) Deficient Mice
    Stanton, Ana Maria
    Aljaibeji, Hayat
    Gholami, Shadi K.
    Parksook, Wasita
    Ding, Miao
    Gomez, Dulce H.
    Romero, Jose R.
    Pojoga, Luminita H.
    Williams, Gordon H.
    Adler, Gail K.
    HYPERTENSION, 2023, 80