PELP1 is a reader of histone H3 methylation that facilitates oestrogen receptor-α target gene activation by regulating lysine demethylase 1 specificity

• Published in: EMBO reports 2010-06, Vol.11 (6), p.438-444
• Main Authors: Nair, Sujit S, Nair, Binoj C, Cortez, Valerie, Chakravarty, Dimple, Metzger, Eric, Schüle, Roland, Brann, Darrell W, Tekmal, Rajeshwar R, Vadlamudi, Ratna K
• Format: Article
• Language: English
• Subjects: Cell Line, Tumor; Co-Repressor Proteins; EMBO09; Estradiol - pharmacology; Estrogen Receptor alpha - metabolism; H3 methylation; Histone Demethylases - metabolism; Histones - metabolism; Humans; KDM1; Methylation - drug effects; PELP1; Promoter Regions, Genetic - genetics; Protein Binding - drug effects; Scientific Report; Scientific Reports; Substrate Specificity - drug effects; Trans-Activators - metabolism; Transcription Factors; Transcriptional Activation - drug effects
• ISSN: 1469-221X; 1469-3178
• DOI: 10.1038/embor.2010.62

Histone methylation has a key role in oestrogen receptor (ERα)‐mediated transactivation of genes. Proline glutamic acid and leucine‐rich protein 1 (PELP1) is a new proto‐oncogene that functions as an ERα 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 ERα target genes, and PELP1 depletion affected the dimethyl histone modifications at ERα 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–ERα–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 ERα target genes. Histone methylation plays a key role in the transcriptional activation of genes. Vadlamudi and co‐workers provide evidence that PELP1, a proto‐oncogene and co‐regulator of ERalpha, interacts with the histone lysine demethylase KDM1 and is a reader of H3 methylation marks. They show that PELP1 alters the substrate specificity of KDM1 and that effective demethylation of H3K9 by KDM1 requires the formation of a KDM1‐ERalpha‐PELP1 complex. These results suggest that PELP1 plays a critical role in modulating the histone code at ERalpha target genes.