LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent rranscription (Nature, 437:436-439, 15 September 2005)

報告日期: 2005/10/28
報告時間: 15:10/16:00
報告學生: 高國勝
講評老師: 蔣輯武
附件下載:

LSD1 demethylates repressive histone marks to promote androgen receptor dependent transcription

Nature 437, 436-439 (2005)

Speaker : 高國勝                                Time : 3:10 PM 2005/10/28

Commentator : 蔣輯武 老師                       Place : Room 602

Abstract :

Various covalent modifications on histones to regulate gene expression alter chromatin structure or serve as binding sites by which other regulatory proteins can be recruited to specific promoters and regulate transcription factors at these sites. One of these modifications is histone methylation. The nuclear receptors, such as the androgen receptor, regulate gene expression through the interaction with chromatin modulating proteins and specific transcription factors. Histone methylation was believed to be irreversible until LSD1 (Lysine-Specific Demethylase) been discovered, that acts as a histone lysine demethylase. In this paper, the authors showed that LSD1 colocalizes with the androgen receptor in normal human prostate and prostate tumour. LSD1 interacted with androgen receptor and stimulated androgen receptor dependent transcription in vitro and in vivo. Otherwise, knockdown of LSD1 protein abrogated androgen induced transcriptional activation and cell proliferation. Chromatin immunoprecipitation analyses demonstrated that androgen receptor and LSD1 form chromatin associated complexes in a ligand dependent manner. LSD1 relieved repressive the histone H3 at lysine 9 residue (H3-K9) by demethylation, thus leading to derepression of androgen receptor target genes. Moreover, they identified pargyline as an inhibitor of LSD1 by blocking demethylation of H3-K9. Here, LSD1 directly associates with demethylation of a repressive histone mark, thus providing a mechanism by which demethylases control specific gene expression.

 

Reference :

Min Gyu Lee, Christopher Wynder, Neil Cooch and Ramin Sheikhattar (2005) An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation. Nature; 437(7057):432-5.

Yujiang Shi, Fei Lan, Caitlin Matson, Peter Mulligan, Johnathan R. Whetstine,Philip A. Cole, Robert A. Casero, and Yang Shi1 (2004) Histone Demethylation Mediated by the Nuclear Amine Oxidase Homolog LSD1 Cell; 119: 941–953