Sugawara M, Scholl T, Ponath P D, Strominger J L
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138.
Mol Cell Biol. 1994 Dec;14(12):8438-50. doi: 10.1128/mcb.14.12.8438-8450.1994.
A novel DNA sequence element termed the J element involved in the regulated expression of class II major histocompatibility complex genes was recently described. To study this element and its role in class II gene regulation further, a cDNA library was screened with oligonucleotide probes containing both the S element and the nearby J element of the human DPA gene. Several DNA clones were obtained by this procedure, one of which, clone 18, is reported and characterized here. It encodes a protein predicted to contain 688 amino acid residues, including 11 zinc finger motifs of the C2H2 type in the C-terminal region, that are Krüppel-like in the conservation of the H/C link sequence connecting them. The 160 N-terminal amino acids in the nonfinger region of clone 18 are highly homologous with similar regions of several other human, mouse, and Drosophila sequences, defining a subfamily of Krüppel-like zinc finger proteins termed TAB (tramtrack [ttk]-associated box) here. One of the Drosophila sequences, ttk, is a developmental control gene, while a second does not contain a zinc finger region but encodes a structure important in oocyte development. An acidic activation domain is located between the N-terminal conserved region of clone 18 and its zinc fingers. This protein appears to require both the S and J elements, which are separated by 10 bp for optimal binding. Antisense cDNA to clone 18 inhibited the expression of a reporter construct containing the DPA promoter, indicating its functional importance in the expression of this class II gene.
最近描述了一种名为J元件的新型DNA序列元件,它参与II类主要组织相容性复合体基因的调控表达。为了进一步研究该元件及其在II类基因调控中的作用,用包含人类DPA基因的S元件和附近J元件的寡核苷酸探针筛选了一个cDNA文库。通过该程序获得了几个DNA克隆,其中一个克隆18在此报告并进行了表征。它编码一种预计含有688个氨基酸残基的蛋白质,在C末端区域包含11个C2H2型锌指基序,在连接它们的H/C连接序列的保守性方面与Krüppel样。克隆18非指状区域的160个N末端氨基酸与其他几种人类、小鼠和果蝇序列的相似区域高度同源,在此定义了一个Krüppel样锌指蛋白亚家族,称为TAB(tramtrack [ttk]相关盒)。果蝇序列之一ttk是一个发育控制基因,而另一个不包含锌指区域,但编码在卵母细胞发育中重要的结构。酸性激活域位于克隆18的N末端保守区域与其锌指之间。这种蛋白质似乎需要S元件和J元件,它们相隔10个碱基对以实现最佳结合。针对克隆18的反义cDNA抑制了包含DPA启动子的报告构建体的表达,表明其在该II类基因表达中的功能重要性。