Graduate Program

Biological Sciences

Degree Name

Master of Science (MS)

Semester of Degree Completion

Spring 2026

Thesis Director

Gary A. Bulla

Thesis Committee Member

Michael W. Beck

Thesis Committee Member

Maryam Rahmati Ishka

Abstract

The goal of the study is to investigate whether the epigenetic modifications can enhance the restoration of liver gene expression in dedifferentiated hepatoma cells or not. For the study, we used dedifferentiated H11 hepatoma cell lines which overexpress one of a panel of introduced candidate liver-enriched transcription factors H11-HNF1a, H11-CREB3L3, H11-CREG1, H11- HHEX, H11-HNF6, and H11-IGFBP1. The cells were treated with the DNA methyltransferase inhibitor 5-azacytidine and the histone deacetylase inhibitor sodium butyrate, both individually and in combination. Gene expression analysis was determined by RT-qPCR, which revealed that while transcription factor overexpression alone produced limited activation, epigenetic modulation, particularly Histone deacetylase inhibition, significantly enhanced the expression of key liver hepatic markers. The strongest responses were seen in H11-HHEX and H11- CREB3L3. DNA methylation resulted in more modest effects. These findings highlight the critical role of chromatin accessibility in regulating the hepatic gene expression. The study further suggests that integrated transcriptional and epigenetic approaches may be essential for restoring liver function. This has important implications for regenerative medicine and differentiation-based cancer therapies.

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