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首页> 外文期刊>Molecular and Cellular Biology >Phylogenetic footprinting reveals a nuclear protein which binds to silencer sequences in the human gamma and epsilon globin genes.
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Phylogenetic footprinting reveals a nuclear protein which binds to silencer sequences in the human gamma and epsilon globin genes.

机译：系统发生的足迹揭示了一种核蛋白，该蛋白与人γ和ε珠蛋白基因的沉默子序列结合。

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Tissue- and developmental stage-specific expression of the human beta-like globin genes is regulated by a combination of ubiquitous and erythroid-restricted trans factors that bind to cis elements near each of the five active genes. Additional interactions of these cis and trans factors with sequences located in the far 5' end of the cluster occur by as yet obscure mechanisms. Because of the complexity of this regulatory puzzle, precise identification of the determinants that control hemoglobin switching has proven difficult. Phylogenetic footprinting is an evolutionary approach to this problem which is based on the supposition that the basic mechanisms of switching are conserved throughout mammalian phylogeny. Alignment of the 5' flanking regions of the gamma genes of several species allows the identification of footprints of 100% conserved sequence. We have now tested oligomers spanning 13 such phylogenetic footprints and find that 12 are bound by nuclear proteins. One conserved element located at -1086 from the gamma genes exhibits repressor activity in transient transfection studies. The protein that binds this element, CSBP-1 (conserved sequence-binding protein 1), also binds at three sites within a silencer element upstream from the epsilon globin gene. Further analysis reveals that the CSBP-1 binding activity is identical to that of a recently cloned zinc finger protein that has been shown to act as a repressor in other systems. The binding of CSPB-1 to silencer sequences in the epsilon and gamma globin genes may be important in the stage-specific silencing of these genes.
机译：人β样球蛋白基因在组织和发育阶段的特异性表达受结合到五个活性基因附近的顺式元件的普遍存在和类红素限制的反式因子的组合调控。这些顺式和反式因子与位于簇的远5'端的序列的其他相互作用是通过尚不清楚的机制发生的。由于这种调节难题的复杂性，已证明很难准确识别控制血红蛋白转换的决定因素。系统发育足迹是解决该问题的一种进化方法，其基于这样的假设，即在整个哺乳动物系统发育过程中，转换的基本机制均得以保留。几种物种的γ基因的5'侧翼区域的比对允许鉴定100％保守序列的足迹。现在，我们已经测试了跨越13个此类系统发育足迹的寡聚体，发现12个被核蛋白结合。位于瞬时基因转染研究中，γ基因中位于-1086处的一个保守元件表现出阻遏物活性。结合该元件的蛋白CSBP-1（保守的序列结合蛋白1）也在ε珠蛋白基因上游的沉默子元件的三个位点结合。进一步的分析表明，CSBP-1的结合活性与最近克隆的锌指蛋白的结合活性相同，后者已被证明在其他系统中起阻遏作用。 CSPB-1与ε和γ珠蛋白基因中的沉默子序列的结合在这些基因的阶段特异性沉默中可能很重要。

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