Condensin and Chromatin Mediated X Chromosome Architecture in Caenorhabditis elegans.

[摘要] Dosage compensation is an essential gene regulatory mechanism that balances X-linked gene expression and X to autosomal expression in organisms that utilize a chromosome-based method of sex determination. In the worm Caenorhabditis elegans dosage compensation is believed to involve two mechanisms. First, upregulation of the X chromosomes occurs in males and hermaphrodites. The mechanism of X upregulation is not know but is believed to balance X-linked gene expression levels to autosomes in males but causes X hyperactivation in hermaphrodites. This necessitates the second mechanism mediated by the activity of the dosage compensation complex (DCC), which downregulates both hermaphrodite X chromosomes by two-fold. The DCC contains a condensin-like complex, condensin IDC, similar to mitotic condensin, suggesting that it may compact the X chromosomes. The goal of my thesis is to address the long-standing hypothesis that DCC activity results in changes in X chromosome structure and explore the highly debated mechanism of X upregulation. In this research, I have uncovered that MYS-1 mediated H4K16ac decondenses the male X chromosome and contributes to upregulation of gene expression on the chromosome. This novel work supports the X upregulation hypothesis. I have also showed that condensin IDC, and the histone modifications regulated by the DCC, mediate interphase X chromosome compaction, providing the first evidence linking condensin-mediated chromosome compaction to chromosome-wide repression of gene expression. My work provided evidence that changes in higher order organization of the X chromosome plays a role both in X upregulation and condensin IDC mediated repression.

[发布机构] University of Michigan

[效力级别] epigenetics

[关键词] dosage compensation;epigenetics;gene expression;chromatin;chromosome territories;caenorhabditis elegans;Molecular;Cellular and Developmental Biology;Science;Molecular, Cellular and Developmental Biology