The HBS1L-MYB intergenic interval associated with elevated HbF levels shows characteristics of a distal regulatory region in erythroid cells

Research output: Contribution to journalArticle

Abstract

HBS1L-MYB intergenic polymorphism (HMIP) on chromosome 6q23 is associated with elevated fetal hemoglobin levels and has pleiotropic effects on several hematologic parameters. To investigate potential regulatory activity in the region, we have measured sensitivity of the sequences to DNase I cleavage that identified 3 tissue-specific DNase I hypersensitive sites in the core intergenic interval. Chromatin immunoprecipitation with microarray (ChIP-chip) analysis showed strong histone acetylation in a defined interval of 65 kb corresponding to the core HBS1L-MYB intergenic region in primary human erythroid cells but not in non-MYB-expressing HeLa cells. ChIP-chip analysis also identified several potential cis-regulatory elements as strong GATA-1 signals that coincided with the DNase I hypersensitive sites present in MYB-expressing erythroid cells. We suggest that HMIP contains regulatory sequences that could be important in hematopoiesis by controlling MYB expression. This study provides the functional link between genetic association of HMIP with control of fetal hemoglobin and other hematologic parameters. We also present a large-scale analysis of histone acetylation as well as RNA polymerase II and GATA-1 interactions on chromosome 6q, and alpha and beta globin gene loci. The data suggest that GATA-1 regulates numerous genes of various functions on chromosome 6q.

Details

Authors
  • Karin Wahlberg
  • Jie Jiang
  • Helen Rooks
  • Kiran Jawaid
  • Fumihiko Matsuda
  • Masao Yamaguchi
  • Mark Lathrop
  • Swee Lay Thein
  • Steve Best
External organisations
  • King's College London
Research areas and keywords

Keywords

  • Acetylation, Chromosomes, Human, Pair 6, DNA, Intergenic, Deoxyribonuclease I, Fetal Hemoglobin, GATA1 Transcription Factor, Gene Expression Regulation, Genes, myb, HeLa Cells, Histones, Humans, K562 Cells, Quantitative Trait Loci, Regulatory Elements, Transcriptional, Journal Article, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)1254-62
Number of pages9
JournalBlood
Volume114
Issue number6
Publication statusPublished - 2009 Aug 6
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes