Date of Completion

12-10-2015

Embargo Period

12-9-2015

Major Advisor

Kent Holsinger

Associate Advisor

Charles Giardina

Associate Advisor

Stormy Chamberlain

Associate Advisor

James Li

Field of Study

Physiology and Neurobiology

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Patterns of neural progenitor division are controlled by a combination of asymmetries in cell division, extracellular signals, and changes in gene expression programs. In a screen for proteins that complex with citron kinase (CitK), a protein essential to cell division in developing brain, I identified the histone methyltransferase- euchromatic histone-lysine N-methyltransferse 2 (G9a). CitK is present in the nucleus and binds to positions in the genome clustered around transcription start sites of genes involved in neuronal development and differentiation. CitK and G9a co-occupy these genomic positions in S/G2-phase of the cell cycle in rat neural progenitors, and CitK functions with G9a to repress gene expression in several developmentally important genes including CDKN1a, H2afz, and Pou3f2/Brn2. The study indicates a novel function for citron kinase in gene repression, and contributes additional evidence to the hypothesis that mechanisms that coordinate gene expression states are directly linked to mechanisms that regulate cell division in the developing nervous system.

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