Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells

Nat Genet. 2010 Jan;42(1):53-61. doi: 10.1038/ng.496. Epub 2009 Dec 13.

Abstract

The discovery of interchromosomal interactions in higher eukaryotes points to a functional interplay between genome architecture and gene expression, challenging the view of transcription as a one-dimensional process. However, the extent of interchromosomal interactions and the underlying mechanisms are unknown. Here we present the first genome-wide analysis of transcriptional interactions using the mouse globin genes in erythroid tissues. Our results show that the active globin genes associate with hundreds of other transcribed genes, revealing extensive and preferential intra- and interchromosomal transcription interactomes. We show that the transcription factor Klf1 mediates preferential co-associations of Klf1-regulated genes at a limited number of specialized transcription factories. Our results establish a new gene expression paradigm, implying that active co-regulated genes and their regulatory factors cooperate to create specialized nuclear hot spots optimized for efficient and coordinated transcriptional control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin Immunoprecipitation
  • Erythroid Cells / cytology
  • Erythroid Cells / metabolism*
  • Fluorescent Antibody Technique
  • Gene Expression Profiling*
  • Gene Regulatory Networks / genetics*
  • Genome-Wide Association Study / methods*
  • Globins / genetics
  • Globins / metabolism
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Biological
  • Oligonucleotide Array Sequence Analysis / methods
  • Protein Binding

Substances

  • Kruppel-Like Transcription Factors
  • erythroid Kruppel-like factor
  • Globins

Associated data

  • GEO/GSE18873