High-resolution analysis of cis-acting regulatory networks at the α-globin locus

Philos Trans R Soc Lond B Biol Sci. 2013 May 6;368(1620):20120361. doi: 10.1098/rstb.2012.0361. Print 2013.

Abstract

We have combined the circular chromosome conformation capture protocol with high-throughput, genome-wide sequence analysis to characterize the cis-acting regulatory network at a single locus. In contrast to methods which identify large interacting regions (10-1000 kb), the 4C approach provides a comprehensive, high-resolution analysis of a specific locus with the aim of defining, in detail, the cis-regulatory elements controlling a single gene or gene cluster. Using the human α-globin locus as a model, we detected all known local and long-range interactions with this gene cluster. In addition, we identified two interactions with genes located 300 kb (NME4) and 625 kb (FAM173a) from the α-globin cluster.

Keywords: chromatin conformation capture; cis-regulatory elements; α-globin locus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCCTC-Binding Factor
  • Chromatin Assembly and Disassembly
  • Chromosomes, Human, Pair 16 / genetics
  • Chromosomes, Human, Pair 16 / metabolism
  • Gene Regulatory Networks
  • Genetic Loci*
  • Genome, Human*
  • Humans
  • Open Reading Frames
  • Promoter Regions, Genetic
  • Protein Interaction Mapping
  • Regulatory Sequences, Nucleic Acid*
  • Repressor Proteins / genetics
  • alpha-Globins / genetics
  • alpha-Globins / metabolism*
  • beta-Globins / metabolism

Substances

  • CCCTC-Binding Factor
  • CTCF protein, human
  • Repressor Proteins
  • alpha-Globins
  • beta-Globins