MOLECULAR GENETICS OF NUCLEOLAR DOMINANCE

核仁优势的分子遗传学

• 批准号: 6031609
• 负责人: CRAIG Stuart PIKAARD
• 金额: $ 21.69万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6031609
• 关键词: Arabidopsis; acetylation; chromatin; chromosomes; cytosine; diploidy; gene expression; gene induction /repression; genetic transcription; histones; hybrid cells; immunoprecipitation; methylation; molecular genetics; polymerase chain reaction; ribosomal RNA; southern blotting; transcription factor

Nucleolar dominance is an epigenetic phenomenon that occurs in both the plant and animal kingdoms and describes the transcription of ribosomal RNA genes inherited from one progenitor, but not the other, in an interspecies hybrid or allopolyploid. It has long been thought that dominant genes are selectively activated. However, recent evidence suggests that under-dominant genes are selectively silenced. Cytosine methylation and histone deacetylation are partners in the repression pathway but it is not known if they act in parallel or in series. It is also not clear if chromatin modifications act on the individual rRNA genes, the multi-megabase chromosomal regions where rRNA genes are clustered (NORs), or other regulatory loci. These questions will be addressed using, as our model system, Arabidopsis suecica, an allotetraploid that combines the genomes of A. thaliana and C. arenosa (also known as A. arenosa) In A. suecica, rRNA genes derived from C. arenosa are transcriptionally active and A. thaliana rRNA genes are silenced. To test the hypothesis that cytosine methylation patterns in the progenitor genomes is needed to establish nucleolar dominance, the A. thaliana cytosine hypomethylation mutant ddm1 will be used as one parent to recreate A. suecica lines. The possibility that histone deacetylation causes cytosine demethylation or that cytosine demethylation causes histone hyperacetylation will be examined to test the hypothesis that these chromatin modifications act in series in the control of nucleolar dominance. The hypothesis that rRNA genes are regulated independent of chromosomal location will be tested by determining if rRNA transgenes at ectopic locations are silenced in newly formed A. suecica lines. In a related aim, we will determine if silencing is restricted to the NORs or if it spreads to neighboring genes adjacent to the NORs. These experiments are part of our long-term effort to understand the positive and negative regulatory mechanisms that control rRNA gene transcription. Understanding nucleolar dominance may also shed light on other epigenetic phenomena such as X-chromosome, provirus, and transposable element inactivation or gametic imprinting. Practical benefits may come from such understanding. For instance, derepression of developmentally silenced genes could have potential for rescuing disease phenotypes due to defects in adult-specific paralogs. Our work on nucleolar dominance is expected to contribute new information to our understanding of chromosomal controls of gene expression.

核仁优势是一种表观遗传现象，发生在植物和动物王国，并描述了转录的核糖体RNA基因遗传自一个祖先，但不是另一个，在种间杂种或异源多倍体。 长期以来，人们一直认为显性基因是被选择性激活的。 然而，最近的证据表明，非显性基因被选择性沉默。 胞嘧啶甲基化和组蛋白去乙酰化是阻遏途径中的伙伴，但不知道它们是平行还是串联作用。 也不清楚染色质修饰是否作用于单个rRNA基因、rRNA基因聚集的多兆染色体区域（NOR）或其他调控位点。 这些问题将被解决，作为我们的模式系统，拟南芥suecica，一个异源四倍体，结合了A。和C. arenosa（也称为A. arenosa）在A. suecica、C. arenosa具有转录活性，A.拟南芥rRNA基因沉默。 为了验证这一假设，即在祖先基因组中胞嘧啶甲基化模式是建立核仁优势所必需的。拟南芥胞嘧啶低甲基化突变体ddm 1将被用作一个亲本来重新产生A.苏西卡线。 组蛋白去乙酰化导致胞嘧啶去甲基化或胞嘧啶去甲基化导致组蛋白超乙酰化的可能性将被检查，以检验这些染色质修饰在核仁优势控制中串联起作用的假设。 rRNA基因的调节与染色体位置无关的假设将通过确定在异位位置的rRNA转基因在新形成的A.苏西卡线。 在一个相关的目标中，我们将确定沉默是否仅限于NORs，或者它是否扩散到与NORs相邻的相邻基因。这些实验是我们长期努力的一部分，以了解控制rRNA基因转录的正调控和负调控机制。 了解核仁优势也可能揭示其他表观遗传现象，如X染色体，原病毒，转座因子失活或配子印记。 这种理解可能带来实际利益。例如，发育沉默基因的去抑制可能具有挽救由于成人特异性旁系同源物缺陷引起的疾病表型的潜力。 我们对核仁优势的研究有望为我们理解染色体控制基因表达提供新的信息。