Lysine-specific histone demethylase 1A

Definition:

Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. Also acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in AR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A. Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1. Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Effector of SNAI1-mediated transcription repression of E-cadherin/CDH1, CDN7 and KRT8. Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7.

References:

[1]. Jing Huang, et al. p53 is regulated by the lysine demethylase LSD1. Nature. 2007 Sep 6;449(7158):105-8. [Content Brief]

[2]. Federico Forneris, et al. Human histone demethylase LSD1 reads the histone code. J Biol Chem. 2005 Dec 16;280(50):41360-5. [Content Brief]

[3]. Yujiang Shi, et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell. 2004 Dec 29;119(7):941-53. [Content Brief]

[4]. Yu-Jiang Shi, et al. Regulation of LSD1 histone demethylase activity by its associated factors. Mol Cell. 2005 Sep 16;19(6):857-64. [Content Brief]

[5]. Min Gyu Lee, et al. An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation. Nature. 2005 Sep 15;437(7057):432-5. [Content Brief]

[6]. Eric Metzger, et al. Phosphorylation of histone H3T6 by PKCbeta(I) controls demethylation at histone H3K4. Nature. 2010 Apr 1;464(7289):792-6. [Content Brief]

[7]. Federico Forneris, et al. Histone demethylation catalysed by LSD1 is a flavin-dependent oxidative process. FEBS Lett. 2005 Apr 11;579(10):2203-7. [Content Brief]

[8]. Yong Chen, et al. Crystal structure of human histone lysine-specific demethylase 1 (LSD1). Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):13956-61. [Content Brief]

[9]. Eric Metzger, et al. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature. 2005 Sep 15;437(7057):436-9. [Content Brief]

[10]. Yiwei Lin, et al. The SNAG domain of Snail1 functions as a molecular hook for recruiting lysine-specific demethylase 1. EMBO J. 2010 Jun 2;29(11):1803-16. [Content Brief]

[11]. Maojun Yang, et al. Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase. Mol Cell. 2006 Aug 4;23(3):377-87. [Content Brief]

[12]. Riccardo Baron, et al. Molecular mimicry and ligand recognition in binding and catalysis by the histone demethylase LSD1-CoREST complex. Structure. 2011 Feb 9;19(2):212-20. [Content Brief]

[13]. Mohamed-Ali Hakimi, et al. A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7420-5. [Content Brief]

[14]. T Lin, et al. Requirement of the histone demethylase LSD1 in Snai1-mediated transcriptional repression during epithelial-mesenchymal transition. Oncogene. 2010 Sep 2;29(35):4896-904. [Content Brief]

[15]. Marcello Tortorici, et al. Protein recognition by short peptide reversible inhibitors of the chromatin-modifying LSD1/CoREST lysine demethylase. ACS Chem Biol. 2013 Aug 16;8(8):1677-82. [Content Brief]

Biomedical Dictionary

The Biomedical Dictionary is a comprehensive and professional collection of biological academic terms and subject datas. All explanations are supported by authoritative books or high impact factor literatures, and you can acquire accurate explanations of the biomedical terms you want to know.

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z #

Name
Email *

	Sorry, but the email address you supplied was invalid.