Retinoblastoma family of proteins and chromatin epigenetics: A repetitive story in a few LINEs

Diego E. Montoya-Durango, Kenneth Ramos

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The retinoblastoma (RB) protein family in mammals is composed of three members: pRB (or RB1), p107, and p130. Although these proteins do not directly bind DNA, they associate with the E2F family of transcription factors which function as DNA sequence-specific transcription factors. RB proteins alter gene transcription via direct interference with E2F functions, as well as recruitment of transcriptional repressors and corepressors that silence gene expression through DNA and histone modifications. E2F/RB complexes shape the chromatin landscape through recruitment to CpG-rich regions in the genome, thus making E2F/RB complexes function as local and global regulators of gene expression and chromatin dynamics. Recruitment of E2F/pRB to the long interspersed nuclear element (LINE1) promoter enhances the role that RB proteins play in genome-wide regulation of heterochromatin. LINE1 elements are dispersed throughout the genome and therefore recruitment of RB to the LINE1 promoter suggests that LINE1 could serve as the scaffold on which RB builds up heterochromatic regions that silence and shape large stretches of chromatin. We suggest that mutations in RB function might lead to global rearrangement of heterochromatic domains with concomitant retrotransposon reactivation and increased genomic instability. These novel roles for RB proteins open the epigenetic-based way for new pharmacological treatments of RB-associated diseases, namely inhibitors of histone and DNA methylation, as well as histone deacetylase inhibitors.

Original languageEnglish (US)
Pages (from-to)233-245
Number of pages13
JournalBiomolecular Concepts
Volume2
Issue number4
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

Fingerprint

Retinoblastoma Protein
Retinoblastoma
Epigenomics
Chromatin
Genes
Gene expression
Histones
Proteins
Transcription Factors
Genome
Co-Repressor Proteins
Retroelements
Histone Deacetylase Inhibitors
Mammals
DNA sequences
DNA
Transcription
Histone Code
Scaffolds
E2F Transcription Factors

Keywords

  • chromatin
  • E2F
  • long interspersed nuclear element (LINE1 or L1)
  • nucleosome
  • retinoblastoma protein family

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cellular and Molecular Neuroscience

Cite this

Retinoblastoma family of proteins and chromatin epigenetics : A repetitive story in a few LINEs. / Montoya-Durango, Diego E.; Ramos, Kenneth.

In: Biomolecular Concepts, Vol. 2, No. 4, 01.08.2011, p. 233-245.

Research output: Contribution to journalArticle

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