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人类中 HMGA1a 识别候选 DNA 序列。

HMGA1a recognition candidate DNA sequences in humans.

机构信息

Division of Gene Expression Mechanism, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.

出版信息

PLoS One. 2009 Nov 24;4(11):e8004. doi: 10.1371/journal.pone.0008004.

Abstract

High mobility group protein A1a (HMGA1a) acts as an architectural transcription factor and influences a diverse array of normal biological processes. It binds AT-rich sequences, and previous reports have demonstrated HMGA1a binding to the authentic promoters of various genes. However, the precise sequences that HMGA1a binds to remain to be clarified. Therefore, in this study, we searched for the sequences with the highest affinity for human HMGA1a using an existing SELEX method, and then compared the identified sequences with known human promoter sequences. Based on our results, we propose the sequences "-(G/A)-G-(A/T)-(A/T)-A-T-T-T-" as HMGA1a-binding candidate sequences. Furthermore, these candidate sequences bound native human HMGA1a from SK-N-SH cells. When candidate sequences were analyzed by performing FASTAs against all known human promoter sequences, 500-900 sequences were hit by each one. Some of the extracted genes have already been proven or suggested as HMGA1a-binding promoters. The candidate sequences presented here represent important information for research into the various roles of HMGA1a, including cell differentiation, death, growth, proliferation, and the pathogenesis of cancer.

摘要

高迁移率族蛋白 A1a(HMGA1a)作为一种结构转录因子,影响着多种正常的生物学过程。它与富含 AT 的序列结合,先前的报告已经证明 HMGA1a 结合到各种基因的真实启动子上。然而,HMGA1a 结合的确切序列仍有待阐明。因此,在这项研究中,我们使用现有的 SELEX 方法搜索与人类 HMGA1a 具有最高亲和力的序列,然后将鉴定出的序列与已知的人类启动子序列进行比较。基于我们的结果,我们提出了“-(G/A)-G-(A/T)-(A/T)-A-T-T-T-”作为 HMGA1a 结合的候选序列。此外,这些候选序列与来自 SK-N-SH 细胞的天然人类 HMGA1a 结合。当通过对所有已知的人类启动子序列进行 FASTA 分析候选序列时,每个序列都命中了 500-900 个序列。提取的一些基因已经被证明或被认为是 HMGA1a 结合的启动子。这里提出的候选序列为研究 HMGA1a 的各种作用提供了重要信息,包括细胞分化、死亡、生长、增殖以及癌症的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0198/2777381/0a597221d4e6/pone.0008004.g001.jpg

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