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Title:Study of meiotic chromosomal structure and molecular mechanisms of meiotic prophase I
Author(s):Xu, Yiding
Advisor(s):Qiao, Huanyu
Contributor(s):Nowak, Romana; Reddi, Prabhakara; Yang, Jing
Department / Program:Comparative Biosciences
Discipline:VMS - Comparative Biosciences
Degree Granting Institution:University of Illinois at Urbana-Champaign
Chromosomal structure
Meiotic prophase I
Abstract:Meiosis is a specialized cell division that produces gametes (sperms and eggs) in sexually reproducing organisms. The prophase I of meiosis is a unique stage, during which pairing and recombination of homologous maternal and parental chromosomes occur. Programed DNA double-strand breaks (DSBs) are generated by SPO11 proteins at the beginning of meiosis. Homologous chromosomes (homologs) first become co-aligned, then, synapse via establishment of a protein complex called synaptonemal complex (SC). DSBs are repaired through homologous recombination (HR). During HR, DNA damage response proteins and other DNA repair proteins are recruited to meiotic DSB sites and results in either non-crossovers or crossovers. A mechanism called meiotic silencing of unsynapsed chromatin (MSUC) silences chromosomes that fail to pair with its homologous partners. A special example of MSUC is meiotic sex chromosome inactivation (MSCI), which specifically silences sex chromosomes in pachytene spermatocytes. During this process, sex chromosomes compact and form a transcriptionally silent nuclear territory named “sex body” or “XY body”. It is critical to understand the molecular and biophysical mechanisms underlying these meiotic events. Liquid-liquid phase separation (LLPS) is a process by which a homogenous aqueous solution demixes into distinct phases. It has emerged as a unifying mechanism in the cell that governs the formation of membraneless organelles and biomolecular compartments. Recent work suggests that the formation of heterochromatin is also driven by LLPS through phase-separating protein HP1. Thus, LLPS is likely a universal mechanism for forming cellular condensates. LLPS has been hypothesized to drive the formation of the Barr body, the inactive X chromosome in female mammals. Here, we addressed the possibility that LLPS underlies the formation of the sex body in spermatocytes. During premeiotic S phase, sister chromatids are formed and held together by cohesin complexes. During meiotic prophase I, chromosomes are organized into compacted loop arrays and exhibit dynamic architectures. Both imaging-based and sequencing-based techniques are developed to study chromosome organizations. Recent advances on chromatin conformation capture (3C)-based methods have shed a new light on the genome-wide chromatin interactions. The reorganization of chromatin architecture during meiotic prophase I has been described. Topologically associating domains (TADs), a typical organization feature of interphase chromosomes, are completely lost at pachytene stage, suggesting meiosis-specific cohesin complexes load onto DNA to form stable loop structures. Interactions between homologs during synapsis are also detected, revealing the juxtaposed arrays of chromatin loops. However, sister chromatids could not be distinguished in paired homologs by traditional Hi-C technique. The recent breakthrough in mitotic study introduced two Hi-C-based approaches that can discriminate the inter- and intra-sister-chromatid interactions in human cancer and yeast cells. It is worthy considering the applications of these methods in meiotic studies. The focus of my thesis is to study the architecture of meiotic chromosomes and the underlying mechanisms of special events during meiotic prophase I. First, I described the work on developing a novel method to study the organization of meiotic chromatin. I demonstrated its feasibility by showing the results from three key steps of the method: the synchronization of spermatogenesis, in-vitro testis culture, and incorporating BrdU during testis culture. Further, I gathered evidence from the literature and hypothesized that LLPS is linked to MSCI and sex-body formation.
Issue Date:2021-08-20
Rights Information:Copyright 2021 Yiding Xu
Date Available in IDEALS:2022-04-29
Date Deposited:2021-12

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