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Identification of sparsely distributed clusters of cis-regulatory elements in sets of co-expressed genes 总被引:4,自引:0,他引:4 下载免费PDF全文
Kreiman G 《Nucleic acids research》2004,32(9):2889-2900
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Crowley EM 《Biopolymers》2001,58(2):165-174
A goal of the human genome project is to determine the entire sequence of DNA (3 x 10(9) base pairs) found in chromosomes. The massive amounts of data produced by this project require interpretation. A Bayesian model is developed for locating regulatory regions in a DNA sequence. Regulatory regions are areas of DNA to which specific proteins bind and control whether or not a gene is transcribed to produce templates for protein synthesis. Each human cell contains the same DNA sequence. Thus the particular function of different cells is determined by the genes that are transcribed in that cell. A Hidden Markov chain is used to model whether a small interval of the DNA is in a regulatory region or not. This can be regarded as a changepoint problem where the changepoints are the start of a regulatory or nonregulatory region. The data consists of protein-binding elements, which are short subsequences, or "words," in the DNA sequence. Although these words can occur anywhere in the sequence, a larger number are expected in regulatory regions. Therefore, regulatory regions are detected by locating clusters of words. For a particular DNA sequence, the model automatically selects those words that best predict regions of interest. Markov chain Monte Carlo methods are used to explore the posterior distribution of the Hidden Markov chain. The model is tested by means of simulations, and applied to several DNA sequences. 相似文献
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In the present study, we have examined the regulation of expression of a newly isolated member of the hsp 30 gene family, hsp 30C. Using RT-PCR, we found that this gene was first heat-inducible at the tailbud stage of development. We also examined the expression of two microinjected modified hsp 30C gene constructs in Xenopus embryos. One of the constructs had 404 bp of hsp 30C 5′-flanking region, whereas the other had 3.6 kb. Both gene constructs had 1 kb of 3′-flanking region. RT-PCR assays were employed to detect the expression of these microinjected genes. The presence of extensive 5′- and 3′-flanking regions of the hsp 30C gene did not confer proper developmental regulation, since heat-inducible expression of both of the microinjected constructs was detectable at the midblastula stage. The premature expression of the microinjected hsp 30 gene was not a result of high plasmid copy number or the presence of plasmid DNA sequences. These results suggest that the microinjected genes contain all the cis-acting DNA sequences required for correct heat-inducible regulation but do not contain the elements required for the proper regulation of hsp 30 gene expression during development. It is possible that regulatory elements controlling the developmental expression of the hsp30 genes may reside upstream or downstream of the entire cluster. © 1993Wiley-Liss, Inc. 相似文献
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原核生物同一种群的每个细胞都是和外界环境直接接触的,它们主要通过开启或关闭某些基因的表达来适应环境条件。所以,环境因子往往是调控的效应因子,必须严格调控转录来确保细胞对环境改变做出有效且充分的反应。原核生物基因的表达受多种因素的调控,而对于大多数细菌来说,调控基因表达的关键步骤是启动子识别和RNA聚合酶启动转录。在细菌的细胞中,可以通过调节RNA聚合酶的活性以及改变RNA聚合酶对启动子的结合来优化基因的转录过程以适应不同环境变化。总结了目前已发现的参与细菌细胞转录调节的各类因子,从这些因子对启动子的作用、RNA聚合酶的作用以及两者的相互作用等方面阐述它们调控基因表达的分子机制。总结多种基因调控的作用,加深对转录起始过程的认识,希望能对未来调控转录起始过程来实现目标基因的高效表达和不利基因的抑制表达提供思路,为以后的工业菌株改造提供依据。 相似文献