PELP1 is a reader of histone H3 methylation that facilitates oestrogen receptor-alpha target gene activation by regulating lysine demethylase 1 specificity.
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.
Nair
Sujit S
SS
Department of Obstetrics and Gynecology, University of Texas Health Science Center in San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229, USA.
Nair
Binoj C
BC
Cortez
Valerie
V
Chakravarty
Dimple
D
Metzger
Eric
E
Schüle
Roland
R
Brann
Darrell W
DW
Tekmal
Rajeshwar R
RR
Vadlamudi
Ratna K
RK
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
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
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