Regulation of major histocompatibility complex class II gene expression, genetic variation and disease.
Regulation of major histocompatibility complex class II gene expression, genetic variation and disease.
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DOI：
10.1038/gene.2009.83
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发表时间：
2010-03
影响因子：
5
通讯作者：
Knight, J. C.
中科院分区：
文献类型：
--
作者：
Handunnetthi, L.;Ramagopalan, S. V.;Ebers, G. C.;Knight, J. C.
主要组织相容性复合体（MHC）II类分子对于适应性免疫应答和维持自身耐受性至关重要。自20世纪70年代初以来，染色体6p21处的MHC II类区域已被证明与大量自身免疫性、炎症性和感染性疾病相关。鉴于大多数MHC II类疾病的关联尚未达到通过单独的结构变异分析的充分解释，在这篇综述中，我们探讨了遗传变异在调节基因表达中的作用。我们描述了MHC II类调控系统的复杂结构，表明其独特的特征可能与观察到的疾病相关。有证据表明，涉及近端启动子序列的单倍型特异性变异可以改变基因表达水平，潜在地改变关键表型性状的出现和表达。虽然很大的重点放在顺式调控元件，我们也探讨了更遥远的增强子元件的作用与动态间和染色体内的相互作用和表观遗传过程的证据。遗传变异在这些机制中的作用可能对常见疾病的易感性产生深远的影响。
Major histocompatibility complex (MHC) class II molecules are central to adaptive immune responses and maintenance of self-tolerance. Since the early 1970s the MHC class II region at chromosome 6p21 has been shown to be associated with a remarkable number of autoimmune, inflammatory and infectious diseases. Given that a full explanation for most MHC class II disease associations has not been reached through analysis of structural variation alone, in this review we explore the role of genetic variation in modulating gene expression. We describe the intricate architecture of the MHC class II regulatory system, indicating how its unique characteristics may relate to observed associations with disease. There is evidence that haplotype-specific variation involving proximal promoter sequences can alter the level of gene expression, potentially modifying the emergence and expression of key phenotypic traits. Although much emphasis has been placed on cis-regulatory elements, we also explore the role of more distant enhancer elements together with the evidence of dynamic inter- and intra-chromosomal interactions and epigenetic processes. The role of genetic variation in such mechanisms may hold profound implications for susceptibility to common disease.
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影响因子：
4.4
作者：
Baecher-Allan, Clare;Wolf, Elizabeth;Haller, David A.
通讯作者：
Haller, David A.
影响因子：
--
作者：
Adamski, J;Ma, ZD;Benveniste, EN
通讯作者：
Benveniste, EN
DOI：
10.1073/pnas.162342499
发表时间：
2002-12-10
影响因子：
11.1
作者：
Burgess-Beusse, B;Farrell, C;Felsenfeld, G
通讯作者：
Felsenfeld, G
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影响因子：
15.3
作者：
Accolla, R S;Jotterand-Bellomo, M;Scarpellino, L;Maffei, A;Carra, G;Guardiola, J
通讯作者：
Guardiola, J
影响因子：
5.8
作者：
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通讯作者：
Nepom, GT