Date of Completion

7-16-2015

Embargo Period

7-16-2015

Keywords

Xlr, Meiosis, SYCP3, Synaptonemal Complex, F8a, X-linked Lymphocyte Regulated, Turner Syndrome, sexbody, testis, spermatogenesis, meiotic drive theory, meiotic sex chromosome inactivation, Xlr3b, Xlr4b, Xlr4c, Slx, Sly, Imprinting Control Region, Differential Methylation, CTCF, sex chromosomes, genomic conflict, PMSC, MSCI, distorter transmission, epigenetics, DNA methylation, CRISPR, ChIP, genomic imprinting

Major Advisor

Dr. Michael J O'Neill

Associate Advisor

Dr. Rachel J. O'Neill

Associate Advisor

Dr. Judy Brown

Field of Study

Genetics and Genomics

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Insight into the Function of X-linked Lymphocyte Regulated 3 (XLR3) and the Mechanism Regulating its Imprinted Expression

Robert J. Foley

University of Connecticut

2015

Abstract

The Synaptonemal Complex Protein 3 (SYCP3), a key component of the synaptonemal complex in mammalian meiosis, has many closely related X-linked homologs on the X chromosome of which the functions are unclear. In rodentia, these genes comprise the Xlr superfamily of proteins and studies elucidating spatial and temporal profiles of these homologs reveal primarily testis specific function. The following study provides evidence for murine testis and ovary function of a newly discovered Xlr superfamily protein, X-linked Lymphocyte Regulated 3 (XLR3). In addition to showing the immunolocalization of the XLR3 protein at the condensed X and Y chromosomes throughout Meiotic Sex Chromosome Inactivation (MSCI), preliminary experiments behind the mechanism controlling expression of the imprinted Xlr3b/4b/4c copies reveals a differentially methylated region (DMR) in the adjacent single copy Factor 8 associated gene A (F8a) consistent with differential binding of the master regulator of chromatin conformation factor CTCF.

Additionally, this work also aims to provide the groundwork for deletion of XLR3 from meiosis to assess its significance in meiotic drive theory, sex chromosome conflict, and infertility. Two similar Xlr superfamily genes, SLX and SLY, whose absence causes near sterility and litter gender bias, have been shown to control gene expression emanating from the sex chromosomes specifically during meiosis. Uncovering the function of these rapidly evolving superfamily proteins in the transmission of the sex chromosomes will add to the growing evidence for a mammalian sex chromosome conflict model of inheritance involving additional layers of gene regulation.

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