Identification of factors mediating the developmental regulation of the early acting -3.9 kb chicken lysozyme enhancer element

P Lefevre, J Kontaraki, Constanze Bonifer

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8 Citations (Scopus)


The chicken lysozyme gene -3.9 kb enhancer forms a DNase I hypersensitive site (DHS) early in macrophage differentiation, but not in more primitive multipotent myeloid precursor cells. A nucleosome becomes precisely positioned across the enhancer in parallel with DHS formation. In transfection assays, the 5'-part of the -3.9 kb element has ubiquitous enhancer activity. The 3'-part has no stimulatory activity, but is necessary for enhancer repression in lysozyme non-expressing cells. Recent studies have shown that the chromatin fine structure of this region is affected by inhibition of histone deacetylase activity after Trichostatin A (TSA) treatment, but only in lysozyme non-expressing cells. These results indicated a developmental modification of chromatin structure from a dynamic, but inactive, to a stabilised, possibly hyperacetylated, active state. Here we have identified positively and negatively acting transcription factors binding to the -3.9 kb enhancer and determined their contribution to enhancer activity. Furthermore, we examined the influence of TSA treatment on enhancer activity in macrophage cells and lysozyme non-expressing cells, including multipotent macrophage precursors. Interestingly, TSA treatment was able to restore enhancer activity fully in macrophage precursor cells, but not in non-macrophage lineage cells. These results suggest (i) that the transcription factor complement of multipotent progenitor cells is similar to that of lysozyme-expressing cells and (ii) that developmental regulation of the -3.9 kb enhancer is mediated by the interplay of repressing and activating factors that respond to or initiate changes in the chromatin acetylation state.
Original languageEnglish
Pages (from-to)4551-60
Number of pages10
JournalNucleic Acids Research
Issue number22
Publication statusPublished - 15 Nov 2001

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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