印记基因DLK1的研究进展

The Research Advance on Imprinted Gene DLK1

在哺乳动物中,有一部分特别的基因,它们由于受到印迹而只表达单一亲本的基因,这种表观遗传的修饰现象就是基因组印记,这有别于经典的孟德尔遗传学定律。DNA甲基化是一种重要的表观遗传修饰,主要的修饰部位发生在DNA的CpG岛,它参与了细胞分化,基因组稳定性、基因印记等多种细胞生物学过程,基因印迹的建立和维持是胚胎正常发育的基础,这一过程的实现有赖于各种DNA甲基化转移酶的精确表达和密切的配合。已发现在哺乳动物的基因组中存在着许多的印记基因,DLK1基因为父系表达母源沉默的印记基因,它的表达同样受到DNA甲基化的调节,它首先在神经母细胞瘤发现并克隆,定位于人类染色体14q32,属于表皮生长因子样超家族的成员之一,约有6个外显子。研究表明,DLK1基因在胚胎肝、早期肌肉组织以及造血干细胞等组织中均有表达,人DLK1基因全长1557bp,编码序列含有1152核苷酸,编码383个氨基酸残基,在人、小鼠、绵羊都存在保守序列,它参与多种细胞的增殖、分化并且与相关肿瘤的发生发展有着密切的关系,印迹基因的印迹异常与肿瘤的易感性及发生发展有重要的关系,本文就国内外DLK1基因的研究进展做一综述。

In mammals, there is a small group of special genes, which are imprinted so that only one of the parental alleles is actually expressed in particular cells. This epigenetic modification of phenomenon is named genomic imprinting, which is far different from the classic mendelian inheritance. In this progress, DNA methylation plays a crucial role in various cell biological of processes such as cell differentiation, cell genomic stability and cell imprinting. The development of the gene imprinting and maintain of the gene imprinting are the fundamental of the normal embryonic growth and development. The realization of this process partly depends on the variety of DNA methylation transferases precise expression and close cooperation. DNA methylation, as the most common forms of epigenetic modification, is an important regulation mechanism ofgenome function. There are a number of genes in our genomes that are subject to genomic imprinting where one parent＇s copy of the gene is expressed while the other is silent. DLK1 （delta drosophila homolog-likel） gene is a paternal expression and maternal silencing of imprinted gene. It is first identified and cloned in the neuroblastoma genes, which is located in the human chromosome 14q32, belongs to one of the number of （Epidermal Growth Factor） EGF-like superfamily. It has approximately six exons. It also expressed in fetal liver, hemopoietic stem cells and early stage muscular tissues, people＇s DLK1 gene has 1557bpDNA. It＇s coding sequence contains 1152 nucleotides, encoding 383 amino acid residues, there are conserved sequences in human, mouse and sheep. It is involved in a variety of cell proliferation, differentiation and with the occurrence of the relevant of tumor development, It is investigated that aberrant imprinting genes are often associated with the susceptibility and development of tumor. In this article, we make a review about the progress of the domestic and foreign research ofDLK1 gene.