Abstract:
:Lysine-Specific Demethylase 1 (LSD1, KDM1A) functions as a transcriptional corepressor through demethylation of histone 3 lysine 4 (H3K4) but has a coactivator function on some genes through mechanisms that are unclear. We show that LSD1, interacting with CoREST, associates with and coactivates androgen receptor (AR) on a large fraction of androgen-stimulated genes. A subset of these AR/LSD1-associated enhancer sites have histone 3 threonine 6 phosphorylation (H3T6ph), and these sites are further enriched for androgen-stimulated genes. Significantly, despite its coactivator activity, LSD1 still mediates H3K4me2 demethylation at these androgen-stimulated enhancers. FOXA1 is also associated with LSD1 at AR-regulated enhancer sites, and a FOXA1 interaction with LSD1 enhances binding of both proteins at these sites. These findings show that LSD1 functions broadly as a regulator of AR function, that it maintains a transcriptional repression function at AR-regulated enhancers through H3K4 demethylation, and that it has a distinct AR-linked coactivator function mediated by demethylation of other substrates.
journal_name
Cell Repjournal_title
Cell reportsauthors
Cai C,He HH,Gao S,Chen S,Yu Z,Gao Y,Chen S,Chen MW,Zhang J,Ahmed M,Wang Y,Metzger E,Schüle R,Liu XS,Brown M,Balk SPdoi
10.1016/j.celrep.2014.11.008subject
Has Abstractpub_date
2014-12-11 00:00:00pages
1618-1627issue
5issn
2211-1247pii
S2211-1247(14)00962-0journal_volume
9pub_type
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