Date of Completion

Spring 5-12-2013

Thesis Advisor(s)

Joseph LoTurco

Honors Major

Biological Sciences


Biology | Cell and Developmental Biology


Regulated repression of gene expression by post-translational modification of histones is required for normal development. The histone methyltransferase G9a is essential for embryonic development, and we have shown that phosphorylation of G9a by the CitK, a gene required for normal CNS development, gates gene repression and dimethylation of histone H3 at lysine 9 (H3K9me2) in neural progenitors. CitK and G9a co-localize to promoter regions of genes up-regulated in CitK null cells. CitK mutant progenitors lack H3K9me2 at promoter regions of up-regulated genes, and re-expression of CitK restores both repression of gene expression and H3K9me2 occupancy. In this thesis we examine the role of the G9a inhibitor Bix-01294 effect on gene expression in neural stem cells. Interestingly, we found that the addition of Bix-01294 causes changes in gene expression that are consistent with changes observed in the null CitK cells. These data support a connection between CitK and its effect on G9a as a means by which neural stem cells regulate gene expression.