Colorado PROFILES, The Colorado Clinical and Translational Sciences Institute (CCTSI)
Keywords
Last Name
Institution

Contact Us
If you have any questions or feedback please contact us.

Chromatin Diminution in Ascaris


Collapse Biography 

Collapse Overview 
Collapse abstract
Genome maintenance and stability are essential, and an organism's genome rarely changes. In striking contrast, chromatin diminution is a programmed process that eliminates specific DNA sequences from the genome. In the parasitic nematode, Ascaris, 25% of the genome is eliminated in the somatic lineages during the 3rd through 5th cleavage (4 to 16 cell stage), while the germline genome remains intact. Both repetitive and unique sequences (genes) are lost during chromatin diminution. The elimination results in chromosome breakage and the loss of chromosome termini as well as the generation of new chromosomes. This process is thought to be a form of gene silencing necessary for development and germline establishment, yet how this programmed elimination contributes to the germline to somatic transition in early Ascaris development remains a mystery more than 100 years after it was discovered. Furthermore, the mechanisms for how chromosomal regions are targeted for elimination, where the sites of chromosomal breakage are located, how DNA breaks are made, what sequences are lost, and how specific sequences are selected to be lost or retained remain unknown. New technologies and approaches will be leveraged to exploit the unique biology and tools in Ascaris to examine chromatin diminution and define eliminated and re-arranged sequences, to examine chromatin modifications associated with diminution, to test a new hypothesis for how eliminated DNA is not segregated during cell division, and to gain additional insight into the potential role of small RNAs in chromatin diminution. We propose that a comprehensive comparison of the somatic and germline genome in Ascaris will permit us to address for the first time a number of central questions regarding diminution including: What rearrangements occur? What genes are lost? Are there common features among the breakpoints that provide insight into how the breakpoints are defined? Are the chromosomal breakpoints at the same approximate location in all individuals or do they vary in different individuals? Furthermore, we propose that epigenetic chromatin changes are associated with the process of diminution and that Ascaris 22G endo-siRNAs and the associated Argonaute CSR-1 RISC complex contribute to chromatin diminution by marking regions of Ascaris chromosomes for retention or elimination. Ascaris is an important human pathogen as it infects over a billion people. Understanding gene maintenance, alterations, and the role of alterations in gene expression in Ascaris is important in understanding the biology of this human parasite. Furthermore, understanding the molecular regulators, mechanism, and consequences of diminution will not only provide insight into DNA elimination and its importance in nematodes, but is likely to increase our understanding of this phenomenon and germline, chromosome, and genome biology in general.
Collapse sponsor award id
R21AI098421

Collapse Time 
Collapse start date
2012-02-15
Collapse end date
2014-01-31

Copyright © 2021 The Regents of the University of Colorado, a body corporate. All rights reserved. (Harvard PROFILES RNS software version: 2.11.1)