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翼状螺旋基因fkh-6和MFH-1的成簇排列:对中胚层发育的潜在影响。

Clustered arrangement of winged helix genes fkh-6 and MFH-1: possible implications for mesoderm development.

作者信息

Kaestner K H, Bleckmann S C, Monaghan A P, Schlöndorff J, Mincheva A, Lichter P, Schütz G

机构信息

Division of Molecular Biology of the Cell I, German Cancer Research Centre, Heidelberg, Germany.

出版信息

Development. 1996 Jun;122(6):1751-8. doi: 10.1242/dev.122.6.1751.

DOI:10.1242/dev.122.6.1751
PMID:8674414
Abstract

The 'winged helix' or 'forkhead' transcription factor gene family is defined by a common 100 amino acid DNA binding domain which is a variant of the helix-turn-helix motif. Here we describe the structure and expression of the mouse fkh-6 and MFH-1 genes. Both genes are expressed in embryonic mesoderm from the headfold stage onward. Transcripts for both genes are localised mainly to mesenchymal tissues, fkh-6 mRNA is enriched in the mesenchyme of the gut, lung, tongue and head, whereas MFH-1 is expressed in somitic mesoderm, in the endocardium and blood vessels as well as the condensing mesenchyme of the bones and kidney and in head mesenchyme. Both genes are located within a 10 kb region (in mouse chromosome 8 at 5.26 +/- 2.56 cM telomeric to Actsk1. The close physical linkage of these two winged helix genes is conserved in man, where the two genes map to chromosome 16q22-24. This tandem arrangement suggests the common use of regulatory mechanisms. The fkh-6/MFH-1 locus maps close to the mouse mutation amputated, which is characterised by abnormal development of somitic and facial mesoderm. Based on the expression patterns we suggest that a mutation in MFH-1, not fkh-6 is the possible cause for the amputated phenotype.

摘要

“翼状螺旋”或“叉头”转录因子基因家族由一个常见的100个氨基酸的DNA结合结构域定义,该结构域是螺旋-转角-螺旋基序的变体。在此,我们描述了小鼠fkh-6和MFH-1基因的结构与表达。这两个基因从头部折叠期开始在胚胎中胚层表达。两个基因的转录本主要定位于间充质组织,fkh-6 mRNA在肠道、肺、舌和头部的间充质中富集,而MFH-1在体节中胚层、心内膜和血管以及骨骼和肾脏的凝聚间充质以及头部间充质中表达。这两个基因都位于一个10 kb的区域内(在小鼠8号染色体上,位于Actsk1端粒5.26 +/- 2.56 cM处)。这两个翼状螺旋基因紧密的物理连锁在人类中也保守存在,这两个基因定位于16号染色体的16q22 - 24区域。这种串联排列表明它们共同使用调控机制。fkh-6/MFH-1基因座定位于靠近小鼠截断突变处,该突变的特征是体节和面部中胚层发育异常。基于表达模式,我们认为截断表型的可能原因是MFH-1而非fkh-6发生了突变。

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