Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates
Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates
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DOI：
10.1101/gr.6086307
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发表时间：
2007-05-01
期刊：
影响因子：
7
通讯作者：
Becker, Thomas S.
中科院分区：
文献类型：
--
作者：
Kikuta, Hiroshi;Laplante, Mary;Becker, Thomas S.
我们报告的证据的机制，为维护长距离保守的同线性脊椎动物基因组。我们发现最大的哺乳动物硬骨鱼保守的染色体片段被跨越高度保守的非编码元件（HCNEs），其发育调控靶基因，和遗传和功能无关的“旁观者”基因。旁观者基因不受驱动靶基因的调控元件的特异性控制，并且以与靶基因不同的模式表达。报告基因插入远端的斑马鱼发育调控基因pax6.1/2，rx 3，id 1和fgf 8和miRNA基因mirn 9 -1和mirn 9 -5概括了这些基因的表达模式，即使位于内部或超出旁观者基因，这表明发育调控基因的调控结构域可以延伸到和超出相邻的转录单位。我们称这些染色体片段为基因组调控块（GRB）。在硬骨鱼类的全基因组复制后，GRB，包括HCNEs和靶基因，通常保持在两个副本中，而旁观者基因通常从一个GRB中丢失，这强烈表明进化压力的作用是保持高等脊椎动物的单拷贝GRB完整。我们发现，损失的旁观者基因和其他突变事件遭受重复GRB硬骨鱼基因组允许靶基因识别和HCNE/靶基因分配。这些研究结果解释了缺乏进化断点从大型脊椎动物染色体片段，并将有助于在人类伽玛射线暴内的位置效应突变的识别。
We report evidence for a mechanism for the maintenance of long-range conserved synteny across vertebrate genomes. We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated "bystander" genes. Bystander genes are not specifically under the control of the regulatory elements that drive the target genes and are expressed in patterns that are different from those of the target genes. Reporter insertions distal to zebrafish developmental regulatory genes pax6.1/2, rx3, id1, and fgf8 and miRNA genes mirn9-1 and mirn9-5 recapitulate the expression patterns of these genes even if located inside or beyond bystander genes, suggesting that the regulatory domain of a developmental regulatory gene can extend into and beyond adjacent transcriptional units. We termed these chromosomal segments genomic regulatory blocks (GRBs). After whole genome duplication in teleosts, GRBs, including HCNEs and target genes, were often maintained in both copies, while bystander genes were typically lost from one GRB, strongly suggesting that evolutionary pressure acts to keep the single-copy GRBs of higher vertebrates intact. We show that loss of bystander genes and other mutational events suffered by duplicated GRBs in teleost genomes permits target gene identification and HCNE/target gene assignment. These findings explain the absence of evolutionary breakpoints from large vertebrate chromosomal segments and will aid in the recognition of position effect mutations within human GRBs.