Differential transcription factor occupancy but evolutionarily conserved chromatin features at the human and mouse M-CSF (CSF-1) receptor loci
Differential transcription factor occupancy but evolutionarily conserved chromatin features at the human and mouse M-CSF (CSF-1) receptor loci
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DOI：
10.1093/nar/gkg804
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发表时间：
2003-10-15
影响因子：
14.9
通讯作者：
Bonifer, C
中科院分区：
文献类型：
--
作者：
Follows, GA;Tagoh, H;Bonifer, C
C-fms基因编码巨噬细胞集落刺激因子受体(M-CSFR或CSF1-R)，是巨噬细胞发育所必需的酪氨酸激酶生长因子受体。我们以前已经描述了小鼠基因的染色质特征；然而，对人类c-FMS基因的染色质结构和功能知之甚少。在这里，我们并排比较了人类和小鼠c-FMS基因座的染色质结构、组蛋白修饰、转录因子占有率和辅因子募集。我们发现，与小鼠基因类似，人c-fms基因具有启动子和内含子增强子元件(c-fms内含子调节元件或FIRE)。这两种分子在进化上都是保守的，并且在巨噬细胞中具有特定的活性。然而，我们通过体内足迹证明，小鼠和人类的c-FMS顺式调控元件都是由一组重叠但不相同的转录因子识别的。尽管有这些差异，染色质免疫沉淀实验显示组蛋白H3修饰的模式非常相似，染色质修饰和重塑活性在单个顺式调控元件和跨c-fms基因座上的分布也相似。我们的实验支持这样的假设，即通过保守的转录因子结合位点的核心，相同的调控原理在两个基因上起作用。
The c-FMS gene encodes the macrophage colony-stimulating factor receptor (M-CSFR or CSF1-R), which is a tyrosine kinase growth factor receptor essential for macrophage development. We have previously characterized the chromatin features of the mouse gene; however, very little is known about chromatin structure and function of the human c-FMS locus. Here we present a side-by-side comparison of the chromatin structure, histone modification, transcription factor occupancy and cofactor recruitment of the human and the mouse c-FMS loci. We show that, similar to the mouse gene, the human c-FMS gene possesses a promoter and an intronic enhancer element (c-fms intronic regulatory element or FIRE). Both elements are evolutionarily conserved and specifically active in macrophages. However, we demonstrate by in vivo footprinting that both murine and human c-FMS cis-regulatory elements are recognised by an overlapping, but non-identical, set of transcription factors. Despite these differences, chromatin immunoprecipitation experiments show highly similar patterns of histone H3 modification and a similar distribution of chromatin modifying and remodelling activities at individual cis-regulatory elements and across the c-FMS locus. Our experiments support the hypothesis that the same regulatory principles operate at both genes via conserved cores of transcription factor binding sites.