FOXL2 inactivation by a translocation 171 kb away:: analysis of 500 kb of chromosome 3 for candidate long-range regulatory sequences
FOXL2 inactivation by a translocation 171 kb away:: analysis of 500 kb of chromosome 3 for candidate long-range regulatory sequences
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DOI：
10.1016/j.ygeno.2003.11.010
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发表时间：
2004-05-01
期刊：
影响因子：
4.4
通讯作者：
Pilia, G
中科院分区：
文献类型：
--
作者：
Crisponi, L;Uda, M;Pilia, G
FOXL 2转录起始点5'端171 kb处的易位断裂点可引起小睑裂/上睑下垂/内眦赘皮综合征（BPES）和相关的卵巢早衰。断裂点福尔斯位于另一个基因MRPS 22内，该基因已在500 kb的连续DNA中测序。MRPS 22编码20个外显子和许多替代转录物。三个CpG岛（>91%相同）之后是非编码外显子4-12和编码外显子13-20。3 'UTR延伸到COPB 2的3' UTR中。基于该序列，三个报道的导致BPES的易位都落在MRPS 22的内含子6内。比较揭示了人类和小鼠内含子6、11和12中的保守片段。值得注意的是，内含子11序列也在山羊PIS综合征（其结合了颅面缺陷、雌性不育和XX性逆转）中缺失。保守序列是模型的候选者，其中它们是远距离增强子或以其他方式影响高阶染色质结构以施加FOXL 2表达的长程顺式调节。(C)2004年爱思唯尔公司All rights reserved.
A translocation breakpoint 171 kb 5' of the transcription start of FOXL2 causes blepharophimosis/ptosis/epicanthus inversus syndrome (BPES) and associated premature ovarian failure. The breakpoint falls within another gene, MRPS22, that has been sequenced in 500 kb of continuous DNA. MRPS22 encodes 20 exons and a number of alternative transcripts. Three CpG islands (>91% identical) are followed by noncoding exons 4-12 and coding exons 13-20. The 3'UTR extends into the 3'UTR of COPB2. Based on the sequence, three reported translocations that cause BPES all fall within intron 6 of MRPS22. Comparisons reveal conserved segments in introns 6, 11, and 12 of human and mouse. Notably intron 11 sequence is also deleted in goat PIS syndrome (which combines craniofacial defects, female infertility, and XX sex reversal). The conserved sequences are candidates for models in which they are distant enhancers or otherwise affect higher order chromatin structure to impose long-range cis regulation of FOXL2 expression. (C) 2004 Elsevier Inc. All rights reserved.