Randhawa G S, Bell D W, Testa J R, Feinberg A P
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Genomics. 1998 Jul 15;51(2):262-9. doi: 10.1006/geno.1998.5370.
The products of histone acetyltransferase and deacetyltransferase genes regulate histone acetylation in eukaryotes, thereby regulating access of transcription factors to chromatin and modulating gene expression. Histone acetylation modifiers have been found to participate as cofactors in diverse mammalian transcriptional complexes involved in regulation of cellular proliferation and differentiation. A role for histone acetylase has been implicated in leukemias and developmental disorders. To gain insight into a role of additional potential histone acetylation modifier genes in human disease, we identified six histone acetyl-transferase or deacetyltransferase homologues using the dbEST database, and we mapped, using high-resolution FISH, a total of five family members to 1p34.3, 6q21-q22, 5q31, 3p24, and 17q21. We then identified human genetic disorders for which candidate genes are not yet known and that have been mapped to the same chromosomal regions as the histone acetylation modifiers. This analysis may help identify new candidate genes for human diseases that involve disturbances of histone acetylation.
组蛋白乙酰转移酶和去乙酰化酶基因的产物在真核生物中调节组蛋白乙酰化，从而调节转录因子与染色质的结合并调控基因表达。已发现组蛋白乙酰化修饰因子作为辅因子参与多种哺乳动物转录复合物，这些复合物参与细胞增殖和分化的调控。组蛋白乙酰化酶在白血病和发育障碍中发挥作用。为深入了解其他潜在的组蛋白乙酰化修饰因子基因在人类疾病中的作用，我们利用dbEST数据库鉴定了六个组蛋白乙酰转移酶或去乙酰化酶同源物，并使用高分辨率荧光原位杂交技术将五个家族成员分别定位到1p34.3、6q21-q22、5q31、3p24和17q21。然后，我们鉴定了尚未确定候选基因且已定位到与组蛋白乙酰化修饰因子相同染色体区域的人类遗传疾病。该分析可能有助于识别涉及组蛋白乙酰化紊乱的人类疾病的新候选基因。
