Developmental activation of the lysozyme gene in chicken macrophage cells is linked to core histone acetylation at its enhancer elements.
Native chromatin IP assays were used to define changes in core histone acetylation at the lysozyme locus during developmental maturation of chicken macrophages and stimulation to high-level expression by lipo-polysaccharide. In pluripotent precursors the lysozyme gene (Lys) is inactive and there is no acetylation of core histones at the gene, its promoter or at the upstream cis-control elements. In myeloblasts, where there is a very low level of Lys expression, H4 acetylation appears at the cis-control elements but not at the Lys gene or its promoter: neither H3 nor H2B become significantly acetylated in myeloblasts. In mature macrophages, Lys expression increases 5-fold: H4, H2B and H2A.Z are all acetylated at the cis-control elements but H3 remains unacetylated except at the -2.4 S silencer. Stimulation with LPS increases Lys expression a further 10-fold: this is accompanied by a rise in H3 acetylation throughout the cis-control elements; H4 and H2B acetylation remain substantial but acetylation at the Lys gene and its promoter remains low. Acetylation is thus concentrated at the cis-control elements, not at the Lys gene or its immediate promoter. H4 acetylation precedes H3 acetylation during development and H3 acetylation is most directly linked to high-level Lys expression.
Myers
Fiona A
FA
Biophysics Laboratories, Institute of Biomedical and Biomolecular Sciences, Faculty of Science, University of Portsmouth, Portsmouth PO1 2DT, UK.
Lefevre
Pascal
P
Mantouvalou
Evangelia
E
Bruce
Kimberley
K
Lacroix
Claire
C
Bonifer
Constanze
C
Thorne
Alan W
AW
Crane-Robinson
Colyn
C
D000107:Acetylation; D000818:Animals; D000906:Antibodies; D002460:Cell Line; D002645:Chickens / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D042381:Granulocyte Precursor Cells / Q000378:metabolism; D006657:Histones / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D009113:Muramidase / Q000235:genetics* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015533:Transcriptional Activation
D000906:Antibodies; D006657:Histones; D012333:RNA, Messenger; D009113:Muramidase