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The nuclear pore complex and chromatin domain dynamics.

机译：核孔复合物和染色质域动力学。

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摘要

The three dimensional organization of chromatin domains in the nucleus is an important factor in gene regulation. In eukaryotic nuclei, transcriptionally silent chromatin clusters at the nuclear periphery while transcriptionally poised chromatin resides in the nuclear interior. Recent studies show that nuclear pore proteins (NUPs) mediate the positioning of genomic loci at the nuclear periphery, specifically to nuclear pore complexes (NPCs), during gene activation. It has also been suggested that tethering of insulator elements to NPCs is an important factor in chromatin insulator function. Here, I investigate the role of NUPs at a native yeast insulator and examine how NPCs affect the intranuclear position of the silent chromatin domain, HMR. I show that while NUPs localize to the native tDNA insulator adjacent to HMR, loss of NUPs does not compromise insulation. On the contrary, I find that NUPs contribute to silencing at native HMR and are able to restore silencing to a de-repressed HMR allele when tethered to the locus, likely via recruitment to the nuclear periphery. I also demonstrate that loss of Nup60 results in decreased peripheral localization of HMR. Furthermore, I show that loss of telomeric tethering pathways does not eliminate Nup60 localization to HMR, and that HMR colocalizes with NPCs when telomeres are not at the periphery, suggesting that NUPs may mediate an independent pathway for HMR association with the nuclear periphery, and specifically NPCs. I propose that localization of NUPs to the tDNA insulator at HMR helps maintain the intranuclear position of the silent locus, which in turn contributes to the fidelity of silencing at HMR.
机译：核染色质域的三维组织是基因调控的重要因素。在真核中，转录沉默染色质聚集在核外围，而转录平衡染色质驻留在核内部。最近的研究表明，核孔蛋白（NUPs）在基因激活过程中介导了基因组位点在核外围的定位，特别是在核孔复合体（NPCs）的定位中。还建议绝缘子元件与NPC的系链是染色质绝缘子功能的重要因素。在这里，我研究了NUP在天然酵母绝缘子上的作用，并研究了NPC如何影响沉默染色质域HMR的核内位置。我表明，尽管NUP定位于与HMR相邻的天然tDNA绝缘子，但NUP的丢失不会损害绝缘。相反，我发现NUP有助于在天然HMR处沉默，并且在拴系到基因位点时，可能通过募集到核周边而将沉默恢复到已抑制的HMR等位基因。我还证明了Nup60的缺失会导致HMR的外周定位降低。此外，我发现端粒连接途径的丧失并不能消除Nup60定位于HMR，并且当端粒不在外围时，HMR与NPC共定位，这表明NUPs可能介导了HMR与核外围结合的独立途径，特别是NPC。我建议将NUPs定位于HMR处的tDNA绝缘子有助于维持沉默基因座的核内位置，从而有助于HMR处的沉默保真度。

著录项

  • 作者

    Ruben, Giulia Jale Gurun.;

  • 作者单位

    University of California, Santa Cruz.;

  • 授予单位 University of California, Santa Cruz.;
  • 学科 Biology Molecular.
  • 学位 Ph.D.
  • 年度 2011
  • 页码 132 p.
  • 总页数 132
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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