Singh P B, Miller J R, Pearce J, Kothary R, Burton R D, Paro R, James T C, Gaunt S J
Department of Molecular Embryology, Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, UK.
Nucleic Acids Res. 1991 Feb 25;19(4):789-94. doi: 10.1093/nar/19.4.789.
Modifiers of position-effect-variegation in Drosophila encode proteins that are thought to modify chromatin, rendering it heritably changed in its expressibility. In an attempt to identify similar modifier genes in other species we have utilized a known sequence homology, termed chromo box, between a suppressor of position-effect-variegation, Heterochromatin protein 1 (HP1), and a repressor of homeotic genes, Polycomb (Pc). A PCR generated probe encompassing the HP1 chromo box was used to clone full-length murine cDNAs that contain conserved chromo box motifs. Sequence comparisons, in situ hybridization experiments, and RNA Northern blot analysis suggest that the murine and human sequences presented in this report are homologues of the Drosophila HP1 gene. Chromo box sequences can also be detected in other animal species, and in plants, predicting a strongly conserved structural role for the peptide encoded by this sequence. We propose that epigenetic (yet heritable) changes in gene expressibility, characteristic of chromosomal imprinting phenomena, can largely be explained by the action of such modifier genes. The evolutionary conservation of the chromo box motif now enables the isolation and study of putative modifier genes in those animal and plant species where chromosomal imprinting has been described.
果蝇中位置效应斑驳的修饰因子编码的蛋白质被认为可修饰染色质，使其在可表达性上发生可遗传的改变。为了在其他物种中鉴定类似的修饰基因，我们利用了已知的序列同源性，即在位置效应斑驳的抑制因子异染色质蛋白1（HP1）和同源异型基因的阻遏物多梳蛋白（Pc）之间存在的所谓染色体框。用聚合酶链反应（PCR）产生的包含HP1染色体框的探针克隆了含有保守染色体框基序的全长小鼠cDNA。序列比较、原位杂交实验和RNA Northern印迹分析表明，本报告中呈现的小鼠和人类序列是果蝇HP1基因的同源物。在其他动物物种和植物中也能检测到染色体框序列，这预示着该序列编码的肽具有高度保守的结构作用。我们提出，基因可表达性的表观遗传（但可遗传）变化，即染色体印记现象的特征，很大程度上可以由这类修饰基因的作用来解释。染色体框基序的进化保守性现在使得能够在已描述染色体印记的动植物物种中分离和研究推定的修饰基因。
