The evolution of the macrophage-specific enhancer (Fms intronic regulatory element) within the CSF1R locus of vertebrates.

The evolution of the macrophage-specific enhancer (Fms intronic regulatory element) within the CSF1R locus of vertebrates.
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DOI:
10.1038/s41598-017-15999-x
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发表时间:
2017-12-07
期刊:
影响因子:
4.6
通讯作者:
Pridans C
Pridans C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hume DA;Wollscheid-Lengeling E;Rojo R;Pridans C

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Csf1r基因座编码巨噬细胞集落刺激因子受体,控制巨噬细胞的增殖、分化和存活。300 bp Fms内含子调控元件(FIRE)位于Csf1r的第二个内含子内,是指导巨噬细胞特异性转录的必要和充分条件。我们分析了脊椎动物中FIRE DNA序列的保存和分化。在爬行动物、鸟类和哺乳动物基因组中,FIRE存在于Csf1r位点的相同位置。基于此元素的最近邻分析在很大程度上概括了从更大的基因组序列数据集推断的系统发育。一个核心元件,包含AP1家族和巨噬细胞特异性转录因子PU.1的结合位点,从蜥蜴到人类都是保守的。在这个元件周围,FIRE序列在进化支中是保守的,其中最保守的元件包含已知髓细胞表达转录因子的基序。相反,AP1/PU之外的分支之间几乎没有对齐。1的元素。该分析倾向于增强子功能的“增强体”和“自助餐”模型之间的混合,在这种模型中,元件合作结合可用转录因子环境的组件。
The Csf1r locus encodes the receptor for macrophage colony-stimulating factor, which controls the proliferation, differentiation and survival of macrophages. The 300 bp Fms intronic regulatory element (FIRE), within the second intron of Csf1r, is necessary and sufficient to direct macrophage-specific transcription. We have analysed the conservation and divergence of the FIRE DNA sequence in vertebrates. FIRE is present in the same location in the Csf1r locus in reptile, avian and mammalian genomes. Nearest neighbor analysis based upon this element alone largely recapitulates phylogenies inferred from much larger genomic sequence datasets. One core element, containing binding sites for AP1 family and the macrophage-specific transcription factor, PU.1, is conserved from lizards to humans. Around this element, the FIRE sequence is conserved within clades with the most conserved elements containing motifs for known myeloid-expressed transcription factors. Conversely, there is little alignment between clades outside the AP1/PU.1 element. The analysis favours a hybrid between “enhanceosome” and “smorgasbord” models of enhancer function, in which elements cooperate to bind components of the available transcription factor milieu.
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发表时间: 2014-12-12
期刊: Science (New York, N.Y.)
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DOI: 10.1093/oxfordjournals.molbev.a004169
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