PgmNr M5063: Genetic studies of large mammalian sex chromosome palindromes harboring testicular germline genes.

Authors:
Q. Ellison; J. Mueller


Institutes
University of Michigan, Ann Arbor, MI.


Abstract:

In placental mammals, the sex chromosomes are enriched for large (>10kb), nearly identical (>99% nucleotide identity), palindromes, which harbor genes expressed during testicular germ cell development. Despite their abundance, the molecular function of these palindromes has not been explored, in part due to their repetitive nature. Y chromosome palindromes are thought to have evolved to facilitate gene conversion between palindrome arms, allowing for the removal of deleterious mutations on the otherwise non-recombining Y chromosome. On the freely recombining X chromosome, an additional function for palindromes is suggested. I propose that the structure of large palindromes may facilitate transcriptional activation of their associated genes during testicular germ cell development.  This proposition is based on the finding that genes associated with sex chromosome palindromes are expressed predominantly or exclusively in post-meiotic testicular germ cells, when single-copy X-linked genes are transcriptionally silenced. To determine whether palindrome structure is necessary for the expression of palindrome-associated genes in post-meiotic testicular germ cells, I am genetically dissecting two distinct mouse X chromosome palindromes using the CRISPR genome engineering technique to flip or delete single palindrome arms.  In mouse lines I have generated that carry either inverted or deleted palindrome arms, I am currently in the process of measuring expression levels of palindrome-associated genes. I will also determine if there are defects in post-meiotic testicular germ cell development.