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

Sujit S. Nair; Binoj C. Nair; Valerie Cortez; Dimple Chakravarty; Eric Metzger; Roland Schüle; Darrell W. Brann; Rajeshwar R. Tekmal; Ratna K. Vadlamudi

doi:10.1038/embor.2010.62

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

Sujit S. Nair, Binoj C. Nair, Valerie Cortez, Dimple Chakravarty, Eric Metzger, Roland Schüle, Darrell W. Brann, Rajeshwar R. Tekmal, Ratna K. Vadlamudi

Neuroscience and Regenerative Medicine

Research output: Contribution to journal › Article › peer-review

89 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	438-444
Number of pages	7
Journal	EMBO Reports
Volume	11
Issue number	6
DOIs	https://doi.org/10.1038/embor.2010.62
State	Published - Jun 2010

Keywords

ER
H3 methylation
KDM1
PELP1

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics

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10.1038/embor.2010.62

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

abstract = "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.",

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AU - Nair, Binoj C.

AU - Cortez, Valerie

AU - Chakravarty, Dimple

AU - Metzger, Eric

AU - Schüle, Roland

AU - Brann, Darrell W.

AU - Tekmal, Rajeshwar R.

AU - Vadlamudi, Ratna K.

PY - 2010/6

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N2 - 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.

AB - 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.

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

Abstract

Keywords

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