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.

译文

天然染色质IP测定法用于定义鸡巨噬细胞发育成熟和脂质多糖刺激高水平表达过程中溶菌酶基因座核心组蛋白乙酰化的变化。在多能前体中,溶菌酶基因 (Lys) 是无活性的,并且在该基因,其启动子或上游顺式控制元件处没有核心组蛋白的乙酰化。在Lys表达水平非常低的成髓细胞中,H4乙酰化出现在顺式控制元件上,但不在Lys基因或其启动子上: H3和H2B在成髓细胞中都没有显着乙酰化。在成熟的巨噬细胞中,Lys表达增加5倍: H4,H2B和H2A.Z在顺式控制元件处均被乙酰化,但H3除在-2.4 S消音器外仍未乙酰化。LPS刺激使Lys表达进一步增加10倍: 伴随着整个顺式控制元件中H3乙酰化的增加; H4和H2B乙酰化仍然很大,但Lys基因及其启动子的乙酰化仍然很低。乙酰化因此集中在顺式控制元件,而不是Lys基因或其直接启动子。在发育过程中,H4乙酰化先于H3乙酰化,而H3乙酰化与高水平Lys表达最直接相关。

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