Llevadot R, Marqués G, Pritchard M, Estivill X, Ferrús A, Scambler P
Molecular Medicine Unit, Institute of the Child Health, London, United Kingdom.
Biochem Biophys Res Commun. 1998 Aug 19;249(2):486-91. doi: 10.1006/bbrc.1998.9165.
The human HIRA gene was identified as a putative transcriptional regulator mapping within the DiGeorge syndrome critical region at 22q11. HIRA-related proteins have been described in a number of species, but functional information concerning family members is only available in Saccharomyces cerevisiae, where the Hir1p and Hir2p proteins are known to be transcriptional corepressors. In order to analyse conservation of HIRA-related genes and to provide resources for functional studies in another model organism we have isolated the HIRA gene from Drosophila melanogaster (dhira). The 3374 nucleotide cDNA encodes a protein of 1047 aa, showing 42% identity with the human protein. Alignment with the predicted HIRA proteins from human, mouse, chick and pufferfish reveals strong conservation within the N-terminal region which contains seven WD domains, with less conservation of C-terminal sequences. In situ hybridisation to salivary gland chromosomes indicates that the gene resides in region 7B2-3 of the X chromosome. Dhira is expressed through embryonic development and at lower levels during larval and pupal development. The expression of dhira is dramatically increased in early embryos and in females, suggesting that the dhira mRNA could be maternally deposited in the embryos.
人类HIRA基因被鉴定为一个假定的转录调节因子，定位于22q11的DiGeorge综合征关键区域内。已在许多物种中描述了与HIRA相关的蛋白质，但仅在酿酒酵母中获得了有关家族成员的功能信息，已知酿酒酵母中的Hir1p和Hir2p蛋白是转录共抑制因子。为了分析与HIRA相关基因的保守性，并为另一种模式生物的功能研究提供资源，我们从黑腹果蝇中分离出了HIRA基因（dhira）。3374个核苷酸的cDNA编码一个1047个氨基酸的蛋白质，与人类蛋白质具有42%的同一性。与来自人类、小鼠、鸡和河豚的预测HIRA蛋白进行比对，结果显示在包含七个WD结构域的N端区域内具有高度保守性，而C端序列的保守性较低。对唾液腺染色体进行原位杂交表明，该基因位于X染色体的7B2 - 3区域。Dhira在胚胎发育过程中表达，在幼虫和蛹发育阶段表达水平较低。Dhira的表达在早期胚胎和雌性中显著增加，这表明dhira mRNA可能是由母体沉积在胚胎中的。
