Condensin and Chromatin Mediated X Chromosome Architecture in Caenorhabditis elegans.

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

Lau, Alyssa C.Buttitta, Laura ;

University of Michigan

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

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/133384/aclau_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 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.