5AFW

Assembly of methylated LSD1 and CHD1 drives AR-dependent transcription and translocation

5AFW の概要

• エントリーDOI: 10.2210/pdb5afw/pdb
• 分子名称: CHROMODOMAIN-HELICASE-DNA-BINDING PROTEIN 1, LYSINE-SPECIFIC HISTONE DEMETHYLASE 1A, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: hydrolase, lsd1k114me2, androgen receptor, chd1, g9a, prostate cancer, tmprrs2-erg
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Nucleus : O14646 O60341
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22725.66

構造登録者

Metzger, E.,Willmann, D.,McMillan, J.,Petroll, K.,Metzger, P.,Gerhardt, S.,vonMaessenhausen, A.,Schott, A.K.,Espejo, A.,Eberlin, A.,Wohlwend, D.,Schuele, K.M.,Schleicher, M.,Perner, S.,Bedford, M.T.,Dengjel, J.,Flaig, R.,Einsle, O.,Schuele, R. (登録日: 2015-01-26, 公開日: 2016-01-13, 最終更新日: 2024-01-10)

主引用文献

Metzger, E.,Willmann, D.,Mcmillan, J.,Forne, I.,Metzger, P.,Gerhardt, S.,Petroll, K.,Von Maessenhausen, A.,Urban, S.,Schott, A.,Espejo, A.,Eberlin, A.,Wohlwend, D.,Schule, K.M.,Schleicher, M.,Perner, S.,Bedford, M.T.,Jung, M.,Dengjel, J.,Flaig, R.,Imhof, A.,Einsle, O.,Schule, R.
Assembly of Methylated Kdm1A and Chd1 Drives Androgen Receptor-Dependent Transcription and Translocation.
Nat.Struct.Mol.Biol., 23:132-, 2016

PubMed Abstract: Prostate cancer evolution is driven by a combination of epigenetic and genetic alterations such as coordinated chromosomal rearrangements, termed chromoplexy. TMPRSS2-ERG gene fusions found in human prostate tumors are a hallmark of chromoplexy. TMPRSS2-ERG fusions have been linked to androgen signaling and depend on androgen receptor (AR)-coupled gene transcription. Here, we show that dimethylation of KDM1A at K114 (to form K114me2) by the histone methyltransferase EHMT2 is a key event controlling androgen-dependent gene transcription and TMPRSS2-ERG fusion. We identified CHD1 as a KDM1A K114me2 reader and characterized the KDM1A K114me2-CHD1 recognition mode by solving the cocrystal structure. Genome-wide analyses revealed chromatin colocalization of KDM1A K114me2, CHD1 and AR in prostate tumor cells. Together, our data link the assembly of methylated KDM1A and CHD1 with AR-dependent transcription and genomic translocations, thereby providing mechanistic insight into the formation of TMPRSS2-ERG gene fusions during prostate-tumor evolution.

PubMed: 26751641
DOI: 10.1038/NSMB.3153

実験手法

X-RAY DIFFRACTION (1.6 Å)