Potential role of a novel transcriptional coactivator PELP1 in histone H1 displacement in cancer cells

Sujit S. Nair, Sandip K. Mishra, Zhibo Yang, Seetharaman Balasenthil, Rakesh Kumar, Ratna K. Vadlamudi

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

The estrogen receptor plays an important role in breast cancer progression. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), also called modulator of nongenomic activity of estrogen receptor (MNAR), a novel coactivator of estrogen receptor, modulates estrogen receptor transactivation functions. The mechanisms by which PELP1 modulates estrogen receptor genomic functions is not known. Here, using biochemical and scanning confocal microscopic analysis, we have demonstrated nuclear localization and functional implications of PELP1. Subnuclear fractionation showed PELP1 association with chromatin and nuclear matrix fractions. Ligand stimulation promoted recruitment of PELP1 to 17β-estradiol responsive promoters, its colocalization with acetylated H3, and increased PELP1-associated histone acetyltransferase enzymatic activity. Far Western analysis revealed that PELP1 interacts with histone 1 and 3, with more preference toward histone 1. Using deletion analysis, we have identified the PELP1 COOH-terminal region as the histone 1 binding site. The PELP1 mutant lacking histone 1-binding domain acts as a dominant-negative and blocks estrogen receptor α-mediated transcription. Chromatin immunoprecipitation analysis showed a cyclic association and dissociation of PELP1 with the promoter, with recruitment of histone 1 and PELP1 occurring in opposite phases. PELP1 overexpression increased the micrococcal nuclease sensitivity of estrogen response element-containing nucleosomes. Our results provide novel insights about the transcription regulation of PELP1 and suggest that PELP1 participates in chromatin remodeling activity via displacement of histone 1 in cancer cells.

Original languageEnglish (US)
Pages (from-to)6416-6423
Number of pages8
JournalCancer Research
Volume64
Issue number18
DOIs
StatePublished - Sep 15 2004
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Nair, S. S., Mishra, S. K., Yang, Z., Balasenthil, S., Kumar, R., & Vadlamudi, R. K. (2004). Potential role of a novel transcriptional coactivator PELP1 in histone H1 displacement in cancer cells. Cancer Research, 64(18), 6416-6423. https://doi.org/10.1158/0008-5472.CAN-04-1786