5AFW: Assembly Of Methylated Lsd1 And Chd1 Drives Ar-dependent Transcription And Translocation

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.
PDB ID: 5AFWDownload
MMDB ID: 135408
PDB Deposition Date: 2015/1/26
Updated in MMDB: 2016/03
Experimental Method:
x-ray diffraction
Resolution: 1.6  Å
Source Organism:
Similar Structures:
Biological Unit for 5AFW: dimeric; determined by software (PISA)
Molecular Components in 5AFW
Label Count Molecule
Proteins (2 molecules)
Chromodomain-helicase-dna-binding Protein 1(Gene symbol: CHD1)
Molecule annotation
Lysine-specific Histone Demethylase 1A(Gene symbol: KDM1A)
Molecule annotation
Chemicals (12 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB