Allele Interactions that Heritably Alter Transcription

遗传性改变转录的等位基因相互作用

• 批准号: 9603638
• 负责人: Vicki Chandler
• 金额: $ 18.44万
• 依托单位: University of Arizona
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9603638&HistoricalAwards=false
• 关键词: Allele; Interactions; Heritably; Alter; Transcription

9603638 Chandler Technical The b regulatory gene of maize encodes a basic-helix-loop-helix protein, which together with other regulatory proteins, activates the transcription of genes encoding the anthocyanin biosynthetic enzymes. Different b alleles activate the pathway in distinct tissues and at different developmental times. Because the alleles are differentially expressed and the amount of pigment produced is a sensitive indicator of regulatory protein levels, such expression can be studied at the plant level. It has been found that specific alleles, when in the same genome with other alleles can alter the second allele in a stable fashion and such alteration cannot be explained by Mendelian concepts. The name given to such phenomena is paramutation. Previous studies have shown that the sequences required for paramutation of b are tightly linked to the locus and lie in the 5' flanking region. However, DNA sequencing and extensive restriction mapping have not identified structural differences between the b alleles undergoing paramutation. Two models are proposed and experiments are devised to test the models. One model is that of unidirectional gene conversion which is consistent with the stability of the altered allele. The other model suggests that changes in chromatin structure may cause the heritable alterations in transcription that occur during paramutation. Questions to be asked are: What cis-acting sequences and other genes participate in paramutation? What cis-acting sites are required for b transcription? Do chromatin, DNA methylation or structural differences correlate with paramutation? Are b sequences in ectopic locations able to participate in paramutation? A variety of mutagenesis strategies are proposed to identify cis-acting sites and trans-acting loci required for the establishment or maintenance of paramutation and for b transcription. Non-technical Transcription can be altered by chromosome position or exposure to alternate alleles, suggesting that genes are not regulated just by local cis-acting sequences and factors that interact with those sequences. Examples of chromatin environments regulating gene expression come from studies of mammalian X-chromosome inactivation, genome imprinting, silencing of yeast mating-type loci, position effect variegation in Drosophila, paramutation and gene silencing in plants. Mechanisms are not understood in any system, although evidence suggests that either DNA or chromatin modification, or both, could be involved. The proposed studies to probe allelic interactions that alter transcription at a corn regulatory gene should help to address this deficiency.

9603638钱德勒 技术 玉米的B调节基因编码碱性螺旋环螺旋蛋白，其与其它调节蛋白一起激活编码花青素苷生物合成酶的基因的转录。不同的B等位基因在不同的组织和不同的发育时期激活该途径。由于等位基因的差异表达和产生的色素的量是一个敏感的指标，调节蛋白质水平，这样的表达可以在植物水平上进行研究。已经发现，特定的等位基因，当与其他等位基因在同一基因组中时，可以以稳定的方式改变第二个等位基因，并且这种改变不能用孟德尔的概念来解释。这种现象被称为顺突变。先前的研究表明，B的副突变所需的序列与该位点紧密相连，位于5'侧翼区。然而，DNA测序和广泛的限制性酶切图谱尚未确定发生副突变的B等位基因之间的结构差异。提出了两个模型，并设计了实验来测试模型。一种模型是单向基因转换，这与改变的等位基因的稳定性一致。另一种模型认为，染色质结构的变化可能导致在副突变过程中发生的转录的遗传性改变。要问的问题是：哪些顺式作用序列和其他基因参与副突变？B转录需要哪些顺式作用位点？染色质、DNA甲基化或结构差异与副突变相关吗？异位位置的B序列是否能够参与副突变？提出了各种诱变策略，以确定建立或维持副突变和B转录所需的顺式作用位点和反式作用位点。 非技术 转录可以通过染色体位置或暴露于替代等位基因而改变，这表明基因不仅仅受到局部顺式作用序列和与这些序列相互作用的因子的调节。调节基因表达的染色质环境的例子来自哺乳动物X染色体失活、基因组印记、酵母交配型位点的沉默、果蝇中的位置效应杂色、植物中的副突变和基因沉默的研究。机制在任何系统中都不清楚，尽管有证据表明可能涉及DNA或染色质修饰，或两者兼而有之。拟议的研究，以探测等位基因的相互作用，改变转录在玉米调控基因应有助于解决这一问题。