title: PELP1 is a reader of histone H3 methylation that facilitates oestrogen receptor-alpha target gene activation by regulating lysine demethylase 1 specificity.
abstract: Histone methylation has a key role in oestrogen receptor (ERalpha)-mediated transactivation of genes. Proline glutamic acid and leucine-rich protein 1 (PELP1) is a new proto-oncogene that functions as an ERalpha co-regulator. In this study, we identified histone lysine demethylase, KDM1, as a new PELP1-interacting protein. These proteins, PELP1 and KDM1, were both recruited to ERalpha target genes, and PELP1 depletion affected the dimethyl histone modifications at ERalpha target genes. Dimethyl-modified histones H3K4 and H3K9 are recognized by PELP1, and PELP1 alters the substrate specificity of KDM1 from H3K4 to H3K9. Effective demethylation of dimethyl H3K9 by KDM1 requires a KDM1-ERalpha-PELP1 functional complex. These results suggest that PELP1 is a reader of H3 methylation marks and has a crucial role in modulating the histone code at the ERalpha target genes.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Health Science Center in San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229, USA.
authors.forename: Sujit S
authors.initials: SS
authors.lastname: Nair
authors.forename: Binoj C
authors.initials: BC
authors.lastname: Nair
authors.forename: Valerie
authors.initials: V
authors.lastname: Cortez
authors.forename: Dimple
authors.initials: D
authors.lastname: Chakravarty
authors.forename: Eric
authors.initials: E
authors.lastname: Metzger
authors.forename: Roland
authors.initials: R
authors.lastname: Schüle
authors.forename: Darrell W
authors.initials: DW
authors.lastname: Brann
authors.forename: Rajeshwar R
authors.initials: RR
authors.lastname: Tekmal
authors.forename: Ratna K
authors.initials: RK
authors.lastname: Vadlamudi
mesh_terms: D045744:Cell Line, Tumor; D056970:Co-Repressor Proteins; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D056466:Histone Demethylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D000090063:Proto-Oncogene Mas; D013379:Substrate Specificity / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D056970:Co-Repressor Proteins; D047628:Estrogen Receptor alpha; D006657:Histones; C000715470:MAS1 protein, human; C438485:PELP1 protein, human; D000090063:Proto-Oncogene Mas; D015534:Trans-Activators; D014157:Transcription Factors; D004958:Estradiol; D056466:Histone Demethylases; C495195:KDM1A protein, human
references.citation: Cell. 2007 Feb 23;128(4):693-705
references.pmid: 17320507
references.citation: Nucl Recept Signal. 2007 May 17;5:e004
references.pmid: 17525794
references.citation: Cell. 2004 Dec 29;119(7):941-53
references.pmid: 15620353
references.citation: Annu Rev Biochem. 2001;70:81-120
references.pmid: 11395403
references.citation: Biochem Pharmacol. 2006 Nov 30;72(11):1589-96
references.pmid: 16844098
references.citation: Nature. 2005 Sep 15;437(7057):436-9
references.pmid: 16079795
references.citation: Mol Cell. 2005 Sep 16;19(6):857-64
references.pmid: 16140033
references.citation: Nature. 2005 Sep 15;437(7057):432-5
references.pmid: 16079794
references.citation: Endocr Relat Cancer. 2009 Jun;16(2):381-9
references.pmid: 19369485
references.citation: Mol Cancer Res. 2008 May;6(5):851-61
references.pmid: 18505929
references.citation: Cell. 2007 Feb 9;128(3):505-518
references.pmid: 17289570
references.citation: Cancer Res. 2004 Sep 15;64(18):6416-23
references.pmid: 15374949
references.citation: Nature. 2007 Aug 9;448(7154):718-22
references.pmid: 17687328
references.citation: J Biol Chem. 2001 Oct 12;276(41):38272-9
references.pmid: 11481323
references.citation: Science. 2008 Jan 11;319(5860):202-6
references.pmid: 18187655