Developmentally regulated recruitment of transcription factors and chromatin remodelling activities to chicken lysozyme cis-regulatory elements in vivo

Research output: Contribution to journalArticle

Authors

  • Pascal Lefevre
  • Svitlana Melnik
  • Nicola Wilson
  • Arthur D Riggs
  • Conny Bonifer

Colleges, School and Institutes

Abstract

Expression of the chicken lysozyme gene is upregulated during macrophage differentiation and reaches its highest level in bacterial lipopolysaccharide (LPS)-stimulated macrophages. This is accompanied by complex alterations in chromatin structure. We have previously shown that chromatin fine-structure alterations precede the onset of gene expression in macrophage precursor cells and mark the lysozyme chromatin domain for expression later in development. To further examine this phenomenon and to investigate the basis for the differentiation-dependent alterations of lysozyme chromatin, we studied the recruitment of transcription factors to the lysozyme locus in vivo at different stages of myeloid differentiation. Factor recruitment occurred in several steps. First, early-acting transcription factors such as NF1 and Fli-1 bound to a subset of enhancer elements and recruited CREB-binding protein. LPS stimulation led to an additional recruitment of C/EBPβ and a significant change in enhancer and promoter structure. Transcription factor recruitment was accompanied by specific changes in histone modification within the lysozyme chromatin domain. Interestingly, we present evidence for a transient interaction of transcription factors with lysozyme chromatin in lysozyme-nonexpressing macrophage precursors, which was accompanied by a partial demethylation of CpG sites. This indicates that a partially accessible chromatin structure of lineage-specific genes is a hallmark of hematopoietic progenitor cells.

Details

Original languageEnglish
Pages (from-to)4386-4400
JournalJournal of Molecular Cell Biology
Volume23
Issue number12
Publication statusPublished - Jun 2003

Keywords

  • chromatin remodelling, chicken lysozyme