Skip to main content
eScholarship
Open Access Publications from the University of California

UCSF

UC San Francisco Electronic Theses and Dissertations bannerUCSF

Investigating the role of a Lamin A-OGT-Emerin axis in female stem cells

Abstract

Lamin A processing is highly regulated, and necessary for proper assembly of the nuclear lamina facilitating its role in nuclear structure and chromatin organization. Pre-lamin A is first farnesylated, and then a short c-terminal peptide is cleaved to produce mature lamin A. O-GlcNAc Transferase (OGT), a glucose sensitive post-translational modification enzyme, has been identified as a potential regulator of lamin A. To explore the role of OGT in lamin A biogenesis, we examined the effects of variation in OGT levels, small molecule inhibition of OGT, and measured tail cleavage efficiency. Mutation of an OGT binding site and O-GlcNAc sites reduced tail cleavage efficiency suggesting that O-GlcNAcylation promotes lamin A processing. However, variation in OGT dose or inhibition of its activity did not alter endogenous lamin A abundance and distribution and did not disrupt differentiation. Likewise, another X-linked gene product, emerin, interacts with lamin A and is O-GlcNAc modified. As the sole developmental difference between XX and XY mESCs is that XX mESC must undergo X-chromosome inactivation (XCI), high expression of X-linked gene products, like emerin, may aid in regulation of XCI. However, perturbations to emerin in XX mESCs do not cause changes in XCI or disrupt epiblast differentiation. These results shed light onto the role of the nuclear lamina and lamin associate proteins in XCI. Additionally, our findings add to our understanding of the regulatory process behind lamin A cleavage and identify a potential link between glucose metabolism and lamina function.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View