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

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)438-444
Number of pages7
JournalEMBO Reports
Volume11
Issue number6
DOIs
StatePublished - Jun 1 2010

Fingerprint

Methylation
Estrogen Receptors
Histones
Transcriptional Activation
Lysine
Genes
Chemical activation
Histone Code
Histone Demethylases
Proto-Oncogenes
human PELP1 protein
Substrate Specificity
Proteins
Substrates

Keywords

  • ER
  • H3 methylation
  • KDM1
  • PELP1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

PELP1 is a reader of histone H3 methylation that facilitates oestrogen receptor-α target gene activation by regulating lysine demethylase 1 specificity. / Nair, Sujit S.; Nair, Binoj C.; Cortez, Valerie; Chakravarty, Dimple; Metzger, Eric; Schüle, Roland; Brann, Darrell W.; Tekmal, Rajeshwar R.; Vadlamudi, Ratna K.

In: EMBO Reports, Vol. 11, No. 6, 01.06.2010, p. 438-444.

Research output: Contribution to journalArticle

Nair, Sujit S. ; Nair, Binoj C. ; Cortez, Valerie ; Chakravarty, Dimple ; Metzger, Eric ; Schüle, Roland ; Brann, Darrell W. ; Tekmal, Rajeshwar R. ; Vadlamudi, Ratna K. / PELP1 is a reader of histone H3 methylation that facilitates oestrogen receptor-α target gene activation by regulating lysine demethylase 1 specificity. In: EMBO Reports. 2010 ; Vol. 11, No. 6. pp. 438-444.
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