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PLoS Genet:新研究为揭示遗传性疾病的发病机制提供希望

来源:生物谷 2014-01-19 23:41

2014年1月19日 讯 /生物谷BIOON/ --近日,来自麦基尔大学等处的研究人员通过研究,揭示了染色质结构对于控制基因活性,尤其是胚胎的正常发育的重要性,相关研究刊登于国际著名遗传学杂志PLoS Genetics上,这项研究对于揭示遗传性疾病的诊断及发病机制有着重要的意义。

机体中的每一个细胞都包含有完整的一套DNA遗传信息,研究者Kmita教授表示,这项工作中我们揭示了控制胚胎发育的基因活性的调节和染色质的三维结构直接相关;实际上染色质的结构可以随着细胞类型不同而改变,因此在调节性DNA序列和其所调节的基因之间就会存在特殊的接触联系。

截至目前,研究遗传性疾病的发病原因主要是通过对DNA的测序和基因序列的分析来解析,然而,某些疾病的原因则必须通过对控制基因表达的DNA序列的研究来揭示。研究者说道,目前我们可以鉴别那些控制给定基因的调节性DNA,而且我们的研究发现为揭示控制染色质结构的机制提供了一定思路,这对于发现并诊断遗传性疾病的原因具有重要的影响。

研究人员的这项研究对于理解很多遗传性疾病的发病机制非常重要,比如和某些疾病相关的Hox基因,比如说遗传性并指病以及生殖畸形综合征等。(生物谷Bioon.com)

Clustering of Tissue-Specific Sub-TADs Accompanies the Regulation of HoxA Genes in Developing Limbs

Berlivet S, Paquette D, Dumouchel A, Langlais D, Dostie J, et al

HoxA genes exhibit central roles during development and causal mutations have been found in several human syndromes including limb malformation. Despite their importance, information on how these genes are regulated is lacking. Here, we report on the first identification of bona fide transcriptional enhancers controlling HoxA genes in developing limbs and show that these enhancers are grouped into distinct topological domains at the sub-megabase scale (sub-TADs). We provide evidence that target genes and regulatory elements physically interact with each other through contacts between sub-TADs rather than by the formation of discreet “DNA loops”. Interestingly, there is no obvious relationship between the functional domains of the enhancers within the limb and how they are partitioned among the topological domains, suggesting that sub-TAD formation does not rely on enhancer activity. Moreover, we show that suppressing the transcriptional activity of enhancers does not abrogate their contacts with HoxA genes. Based on these data, we propose a model whereby chromatin architecture defines the functional landscapes of enhancers. From an evolutionary standpoint, our data points to the convergent evolution of HoxA and HoxD regulation in the fin-to-limb transition, one of the major morphological innovations in vertebrates.

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