The Role of CREG1 as a Master Regular of Liver Function

Abstract

Mammalian development involves a complex system of regulatory signals and reactions resulting in highly differentiated cell types with specific structure and function. The liver is a major organ that has been studied extensively to understand underlying genetic processes responsible for specification, establishment and maintenance of tissue identity. Hepatoma and hepatoma variant cell lines have been used as a model to understand genetic networks responsible for liver function. Whole genome microarray analysis of hepatocyte cell lines has revealed candidate genes that may serve as regulators or master regulators of liver specificity. In two previous studies, the role of candidate gene Cellular Repressor of E1A Stimulated Gene (CREG1) on regulation of liver‐specific gene expression was determined using transfection studies combined with utilization of quantitative real‐time polymerase chain reaction (qRTPCR). Both studies found strong activation (10–100‐fold) of transcription factor Hnf6 and the downstream gene Serpina1 (a marker gene used to identify liver function). These findings suggested that CREG1 might act through Hnf6 to regulate Serpina1 via a Locus Control Region (LCR). However, while one study showed that of CREG1 overexpression in a hepatoma variant cell line resulted in modest activation of liver‐specific transcription factors Hnf1, Hnf4 and Hnf3, the second study suggested robust activation of these genes as measured by qRT‐PCR. In the current study, a CREG1 expression vector was reintroduced into two variant cell lines and gene activation profiles monitored to establish validity of the previous studies. However, we postulated that CREG‐1 overexpression, validated by qRT‐PCR, can activate expression of hepatocyte transcription factor Hnf6 and the downstream gene Serpina1.However, analysis of gene silencing of liver and non‐liver cell types using whole genome microarray screening will help to identify, compare and elucidate the effects of various candidate tissue specific genes. Moreover, we are currently interested to see the reintroduction of liver‐enriched factors in hepatoma variants fully reactivates liver gene expression. Thus, understanding the underlying mechanism and role of each gene helps to develop therapeutic treatment targets for treating liver diseases.Support or Funding InformationEastern Illinois University, Department of Biological ScienceThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.