A histone map of human chromosome 20q13.12

PLoS One. 2009;4(2):e4479. doi: 10.1371/journal.pone.0004479. Epub 2009 Feb 20.

Abstract

Background: We present a systematic search for regulatory elements in a 3.5 Mb region on human chromosome 20q13.12, a region associated with a number of medical conditions such as type II diabetes and obesity.

Methodology/principal findings: We profiled six histone modifications alongside RNA polymerase II (PolII) and CTCF in two cell lines, HeLa S3 and NTERA-2 clone D1 (NT2/D1), by chromatin immunoprecipitation using an in-house spotted DNA array, constructed with 1.8 kb overlapping plasmid clones. In both cells, more than 90% of transcription start sites (TSSs) of expressed genes showed enrichments with PolII, di-methylated lysine 4 of histone H3 (H3K4me2), tri-methylated lysine 4 of histone H3 (H3K4me3) or acetylated H3 (H3Ac), whereas mono-methylated lysine 4 of histone H3 (H3K4me1) signals did not correlate with expression. No TSSs were enriched with tri-methylated lysine 27 of histone H3 (H3K27me3) in HeLa S3, while eight TSSs (4 expressed) showed enrichments in NT2/D1. We have also located several CTCF binding sites that are potential insulator elements.

Conclusions/significance: In summary, we annotated a number of putative regulatory elements in 20q13.12 and went on to verify experimentally a subset of them using dual luciferase reporter assays. Correlating this data to sequence variation can aid identification of disease causing variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCCTC-Binding Factor
  • Cell Line
  • Chromatin Immunoprecipitation
  • Chromosome Mapping / methods*
  • Chromosomes, Human, Pair 20*
  • DNA-Binding Proteins / analysis
  • Enhancer Elements, Genetic
  • Histones*
  • Humans
  • Methylation
  • RNA Polymerase II / analysis
  • Repressor Proteins / analysis

Substances

  • CCCTC-Binding Factor
  • CTCF protein, human
  • DNA-Binding Proteins
  • Histones
  • Repressor Proteins
  • RNA Polymerase II