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锌转录调控元件的基因组特征揭示了 ZNF658 的潜在功能作用。

Genomic Characterization of the Zinc Transcriptional Regulatory Element Reveals Potential Functional Roles of ZNF658.

机构信息

Department of Foods and Nutrition, University of Georgia, Athens, GA, USA.

Department of Statistics, University of Georgia, Athens, GA, USA.

出版信息

Biol Trace Elem Res. 2019 Dec;192(2):83-90. doi: 10.1007/s12011-019-1650-9. Epub 2019 Feb 7.

DOI:10.1007/s12011-019-1650-9
PMID:30734197
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6685770/
Abstract

The zinc transcriptional regulatory element (ZTRE) is a newly reported binding motif for human zinc finger protein ZNF658, which alters gene expression in response to cellular zinc. The ZTRE has two nucleotide components-the palindromic flanking pairs and the bridging "N" bases between these flanks that range in number from 0 to 100. There are 12 pairs of ZTRE flanks (designated A-L). Three thousand five hundred twenty-five genes contain one or more ZTREs - 1000 to + 200 bp from their transcriptional start site (TSS). ZTRE-E is observed at a greater frequency, and ZTRE containing 25 bridging bases are less frequent, within - 200 bp from the TSS. The genes with ZTREs in this range are enriched in processes that may compensate zinc deficiency, while other genes with ZTREs outside this range are enriched in transcriptional activation processes. The division of ZTREs into two groups may imply a dual role of ZNF658, similar to the homologous yeast protein Zap1, via binding to low or high affinity sequences dependent upon cellular zinc. The KLF/Sp1-family binding motif is prevalent within the ZTRE "N" bridging bases, suggesting ZNF658 may compete with Sp1-like transactivators to suppress transcription.

摘要

锌转录调控元件 (ZTRE) 是一种新报道的人类锌指蛋白 ZNF658 的结合基序,它可响应细胞内锌来改变基因表达。ZTRE 有两个核苷酸组成部分——回文侧翼对和这些侧翼之间的桥接“N”碱基,数量从 0 到 100 不等。有 12 对 ZTRE 侧翼(指定为 A-L)。3525 个基因在其转录起始位点 (TSS) 上下游 1000 到+200bp 处含有一个或多个 ZTRE。在 TSS 上下游-200bp 处,观察到 ZTRE-E 的频率更高,而含有 25 个桥接碱基的 ZTRE 则较少。在此范围内含有 ZTRE 的基因在可能补偿锌缺乏的过程中富集,而在此范围之外的其他含有 ZTRE 的基因则在转录激活过程中富集。将 ZTRE 分为两组可能意味着 ZNF658 的双重作用,类似于同源酵母蛋白 Zap1,通过与细胞内锌依赖的低或高亲和力序列结合来实现。KLF/Sp1 家族结合基序在 ZTRE“N”桥接碱基中普遍存在,表明 ZNF658 可能与 Sp1 样转录激活因子竞争以抑制转录。

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