Dataset Information

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.

SUBMITTER: Nair SS

PROVIDER: S-EPMC2892318 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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

Nair Sujit S SS 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

EMBO reports 20100507 6

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- ...[more]

PMID: 20448663

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Project description:Patterns of methylation at lysine 4 and 27 of histone H3 have been associated with states of gene activation and repression that are developmentally regulated and are thought to underlie the establishment of lineage specific gene expression programs. Recent studies have provided fundamental insight into the problem of lineage specification by comparing global changes in chromatin and transcription between ES and neural stem (NS) cells, points respectively of departure and arrival for neural commitment. With these maps of the differentiated state in place, a central task is now to unravel the chromatin dynamics that enables these differentiation transitions. In particular, the observation that lineage-specific genes repressed in ES cells by Polycomb-mediated H3-K27 trimethylation (H3-K27me3) are demethylated and derepressed in differentiated cells posited the existence of a specific H3-K27 demethylase.In order to gain insight into the epigenetic transitions that enable lineage specification, we investigated the early stages of neural commitment using as model system the monolayer differentiation of mouse ES cells into neural stem (NS) cells. Starting from a comprehensive profiling of JmjC-domain genes, we report here that Jmjd3, recently identified as a H3-K27me3 specific demethylase, controls the expression of key regulators and markers of neurogenesis and is required for commitment to the neural lineage.Our results demonstrate the relevance of an enzymatic activity that antagonizes Polycomb regulation and highlight different modalities through which the dynamics of H3-K27me3 is related to transcriptional output. By showing that the H3-K27 demethylase Jmjd3 is required for commitment to the neural lineage and that it resolves the bivalent domain at the Nestin promoter, our work confirms the functional relevance of bivalent domain resolution that had been posited on the basis of the genome-wide correlation between their controlled resolution and differentiation. In addition, our data indicate that the regulation of H3-K27me3 is highly gene- and context- specific, suggesting that the interplay of methyltransferases and demethylases enables the fine-tuning more than the on/off alternation of methylation states.

Dataset Information

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

Publications

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

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