The Pole3 bidirectional unit is regulated by MYC and E2Fs

Gene. 2006 Jan 17;366(1):109-16. doi: 10.1016/j.gene.2005.07.046. Epub 2006 Jan 3.

Abstract

Pole3 (DPB4/YBL1/CHRAC17) is one of the subunits of the DNA polymerase e. It contains a histone-like domain required for the hererodimerization with its Pole4 (DPB3) partner. In another interaction, Pole3 heterodimerizes with YCL1/CHRAC15 and associates with the ACF1/SNF2H remodelling complex. We find that the Pol3 gene is regulated in starved NIH3T3 fibroblasts upon induction with serum, with a peak at the entry in the S phase. We characterized the Pole3 promoter, which is linked bidirectionally to C9Orf46, a gene of unknown function: it has no CCAAT nor TATA-boxes, and contains an E box and two potential E2F sites. Mutagenesis analysis points to a minimal promoter region as sufficient for activation; the E box and a neighbouring direct repeat are important for regulation. Cell-cycle regulation was reproduced in stable clones and an additional E2F site was found to be important. Chromatin immunoprecipitation analysis indicates that E2F1/4, as well as MYC, are associated with the Pole3 promoter in a phase-specific way. These data highlight coregulation of a histone-like gene with core histones upon DNA synthesis, and represent a first dissection of the interplay between two essential cell-cycle regulators on a bidirectional promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin Immunoprecipitation / methods
  • DNA Polymerase II / biosynthesis*
  • DNA Polymerase II / genetics
  • Gene Expression Regulation / physiology*
  • Histones / biosynthesis
  • Histones / genetics
  • Mice
  • Mutagenesis / genetics
  • NIH 3T3 Cells
  • Point Mutation
  • Poly-ADP-Ribose Binding Proteins
  • Protein Structure, Tertiary / genetics
  • Response Elements / genetics
  • S Phase / physiology*
  • TATA Box / genetics
  • Transcription, Genetic / physiology*

Substances

  • Histones
  • Poly-ADP-Ribose Binding Proteins
  • DNA Polymerase II
  • Pole protein, mouse