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通过计算机模拟分析挖掘哺乳动物中染色质介导的Hox基因调控的潜在顺式作用元件。

Mining of putative cis-acting elements for chromatin mediated regulation of Hox genes in mammals by in-silico analysis.

作者信息

Bengani Hemant, Ganapathi Mythily, Singh Gajinder Pal, Brahmachari Vani

机构信息

Dr. B.R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, India.

出版信息

J Exp Zool B Mol Dev Evol. 2007 Jul 15;308(4):384-95. doi: 10.1002/jez.b.21162.

Abstract

The remarkable conservation in developmental strategies across phyla is well reflected in the conservation of the homeotic gene complexes responsible for establishing the body plan in embryonic development. On the other hand, changes in the strategy of transcription regulation are believed to form one of the major factors in the evolution of developmental mechanisms and phenotypic evolution of species. Apart from transcription regulation by gene specific transcription factors, the role of regulators mediating modifications of chromatin proteins, especially of HOX gene clusters in Drosophila is well documented. By comparative genomics we have identified novel motifs conserved in mouse, chimpanzee and human in the noncoding upstream/intronic sequences of Hox genes by in silico analysis. These motifs lack the binding sites for known transcription factors and are significantly over represented in the target genes of one of the core components of Polycomb Repressive Complex namely Supressor of zeste 12 (SUZ12) in human embryonic cells reported by Lee et al. [2006a. Cell 125:301-313]. Therefore, we predict that they could be the sites of interaction of chromatin modifying complexes for epigenetic regulation.

摘要

跨门的发育策略中的显著保守性在负责胚胎发育中身体蓝图建立的同源异型基因复合体的保守性中得到了很好的体现。另一方面,转录调控策略的变化被认为是发育机制进化和物种表型进化的主要因素之一。除了基因特异性转录因子的转录调控外,介导染色质蛋白修饰的调节因子的作用,特别是果蝇中HOX基因簇的作用,已有充分的文献记载。通过比较基因组学,我们通过计算机分析在小鼠、黑猩猩和人类的Hox基因非编码上游/内含子序列中鉴定出了新的保守基序。这些基序缺乏已知转录因子的结合位点,并且在Lee等人[2006a. Cell 125:301 - 313]报道的人类胚胎细胞中,在多梳抑制复合体的核心成分之一即zeste 12抑制因子(SUZ12)的靶基因中显著富集。因此,我们预测它们可能是用于表观遗传调控的染色质修饰复合体的相互作用位点。

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