Dynamic changes in the genomic localization of DNA replication-related element binding factor during the cell cycle

Cell Cycle. 2013 May 15;12(10):1605-15. doi: 10.4161/cc.24742. Epub 2013 Apr 25.

Abstract

DREF was first characterized for its role in the regulation of transcription of genes encoding proteins involved in DNA replication and found to interact with sequences similar to the DNA recognition motif of the BEAF-32 insulator protein. Insulators are DNA-protein complexes that mediate intra- and inter-chromosome interactions. Several DNA-binding insulator proteins have been described in Drosophila, including BEAF-32, dCTCF and Su(Hw). Here we find that DREF and BEAF-32 co-localize at the same genomic sites, but their enrichment shows an inverse correlation. Furthermore, DREF co-localizes in the genome with other insulator proteins, suggesting that the function of this protein may require components of Drosophila insulators. This is supported by the finding that mutations in insulator proteins modulate DREF-induced cell proliferation. DREF persists bound to chromatin during mitosis at a subset of sites where it also co-localizes with dCTCF, BEAF-32 and CP190. These sites are highly enriched for sites where Orc2 and Mcm2 are present during interphase and at the borders of topological domains of chromosomes defined by Hi-C. The results suggest that DREF and insulator proteins may help maintain chromosome organization during the cell cycle and mark a subset of genomic sites for the assembly of pre-replication complexes and gene bookmarking during the M/G1 transition.

Keywords: cell cycle; chromatin; epigenetics; mitosis; replication; transcription.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Chromatin / metabolism
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila
  • Drosophila Proteins / analysis*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Eye Proteins / analysis
  • Eye Proteins / genetics
  • Eye Proteins / metabolism
  • Genome*
  • Insulator Elements / genetics
  • Interphase
  • Microtubule-Associated Proteins / analysis
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Minichromosome Maintenance Proteins / metabolism
  • Mitosis
  • Mutation
  • Nuclear Proteins / analysis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Origin Recognition Complex / metabolism
  • Transcription Factors / analysis*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • BEAF-32 protein, Drosophila
  • CP190 protein, Drosophila
  • Chromatin
  • DNA-Binding Proteins
  • Dref protein, Drosophila
  • Drosophila Proteins
  • Eye Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • Orc2 protein, Drosophila
  • Origin Recognition Complex
  • Transcription Factors
  • MCM2 protein, Drosophila
  • Minichromosome Maintenance Proteins

Associated data

  • GEO/GSE39664