Gelinas R, Endlich B, Pfeiffer C, Yagi M, Stamatoyannopoulos G
Nature. 1985;313(6000):323-5. doi: 10.1038/313323a0.
The sequence 5'TTGGPyCAAT 3' (the 'CCAAT box') is a constituent of the promoter region of many eukaryotic and prokaryotic genes and is believed to play a part in promoter function. A characteristic of the two fetal human globin genes (A gamma and G gamma) is a duplication of a 12-base pair (bp) sequence containing the CCAAT box. Here we report a G----A substitution in the TTG sequence of the distal CCAAT box of the A gamma-globin gene in an individual with the A gamma (Greek) type of hereditary persistence of fetal haemoglobin (HPFH). This represents the first report of a natural mutation of the CCAAT box in a eukaryotic gene. The fact that this transition is associated with inappropriate expression of the A gamma gene in adult life suggests that the CCAAT box (or its surrounding sequences) may have a role in the developmental control of gamma-globin genes.
序列5'TTGGPyCAAT 3'（“CCAAT框”）是许多真核生物和原核生物基因启动子区域的一个组成部分，并且被认为在启动子功能中发挥作用。人类胎儿的两种珠蛋白基因（Aγ和Gγ）的一个特点是含有CCAAT框的12个碱基对（bp）序列发生了重复。在此，我们报告了一名患有Aγ（希腊型）遗传性胎儿血红蛋白持续存在（HPFH）的个体中，Aγ珠蛋白基因远端CCAAT框的TTG序列发生了G→A替换。这是真核生物基因中CCAAT框自然突变的首次报道。这种转换与成年期Aγ基因的异常表达相关，这一事实表明CCAAT框（或其周围序列）可能在γ珠蛋白基因的发育调控中发挥作用。
