Johnson C A, Barlow A L, Turner B M
Department of Anatomy, Medical School, University of Birmingham, UK.
Gene. 1998 Oct 9;221(1):127-34. doi: 10.1016/s0378-1119(98)00435-1.
The steady-state level of histone acetylation in eukaryotes is established and maintained by multiple histone acetyltransferases (HATs) and histone deacetylases (HDACs) and affects both the structure and the function of chromatin. Histone deacetylases play a key role in the regulation of transcription, and form a highly conserved protein family in many eukaryotic species. Here we describe the cloning, sequencing and genetic mapping of two histone deacetylase genes in Drosophila melanogaster: dHDAC1 is essentially identical to the previously cloned D. melanogaster d-Rpd3 gene and dHDAC3, a novel gene, is orthologous to the human and the chicken (Gallus gallus) HDAC3 genes. The predicted amino acid sequence (438 aa) of dHDAC3 shows 58.1% identity with dHDAC1/d-Rpd3, the only previously known member of the HDAC family in this organism. The map positions on polytene chromosomes for dHDAC1 and dHDAC3 were determined as 64C1-6 and 83A3-4 respectively. A search for other dHDAC3-like genes failed to find other potential paralogues in D. melanogaster, but identified significant homologies with bacterial and fungal genes encoding enzymes that metabolise acetyl groups, and with genes for other hydrolyases such as carboxypeptidase. In addition, histone deacetylase activity in D. melanogaster nuclear extracts can be inhibited by high concentrations of zinc and activated by low concentrations, which is identical to the properties of bovine carboxypeptidase A. On the basis of sequence and functional similarities, we suggest that histone deacetylases are metal-substituted enzymes.
真核生物中组蛋白乙酰化的稳态水平由多种组蛋白乙酰转移酶（HATs）和组蛋白脱乙酰酶（HDACs）建立并维持，且会影响染色质的结构与功能。组蛋白脱乙酰酶在转录调控中起关键作用，在许多真核生物物种中构成一个高度保守的蛋白家族。在此，我们描述了黑腹果蝇中两个组蛋白脱乙酰酶基因的克隆、测序及基因定位：dHDAC1与先前克隆的黑腹果蝇d-Rpd3基因基本相同，而dHDAC3是一个新基因，与人及鸡（原鸡）的HDAC3基因是直系同源的。dHDAC3预测的氨基酸序列（438个氨基酸）与dHDAC1/d-Rpd3有58.1%的同一性，dHDAC1/d-Rpd3是该生物体中HDAC家族此前唯一已知的成员。dHDAC1和dHDAC3在多线染色体上的定位分别确定为64C1-6和83A3-4。对其他类似dHDAC3基因的搜索未能在黑腹果蝇中找到其他潜在的旁系同源物，但发现与编码代谢乙酰基的酶的细菌和真菌基因以及其他水解酶如羧肽酶的基因有显著同源性。此外，高浓度的锌可抑制黑腹果蝇核提取物中的组蛋白脱乙酰酶活性，低浓度则可激活该活性，这与牛羧肽酶A的特性相同。基于序列和功能相似性，我们认为组蛋白脱乙酰酶是金属取代酶。
