Liver progenitor cells may construct cysts having heterogeneous gene expression of liver-enriched transcription factors in mice with conditional knockout of the Hhex gene.

The deletion of the Hhex (Hematopoietically expressed homeobox) gene causes agenesis of the liver and polycystic liver disease depending on its timing. The present study was undertaken to determine the role of the Hhex gene in not only signaling cascades to cyst and abnormal bile duct formation but also the liver progenitor contribution to cystic development. Liver-specific Hhex knockout mice (Alb-Cre/Hhex) in adult stages were used.

Analysis of regulatory mechanisms of an insulin-inducible SHARP-2 gene by (S)-Equol.

Small compounds that activate the insulin-dependent signaling pathway have potential therapeutic applications in controlling type 2 diabetes mellitus. The rat enhancer of split- and hairy-related protein-2 (SHARP-2) is an insulin-inducible transcription factor that decreases expression of the phosphoenolpyruvate carboxykinase gene, a gluconeogenic enzyme gene. In this study, we screened for soybean isoflavones that can induce the rat SHARP-2 gene expression and analyzed their mechanism(s).

(-)-Epigallocatechin-3-gallate enhances the expression of an insulin-inducible transcription factor gene via a phosphoinositide 3-kinase/atypical protein kinase C lambda pathway.

The rat enhancer of split- and hairy-related protein-1 (SHARP-1) is an insulin-inducible transcriptional repressor. In this study, we examined issues of whether (-)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, regulates the expression of the rat SHARP-1 gene and which signaling pathway mediates the regulation. When H4IIE cells were treated with EGCG, SHARP-1 mRNA levels rapidly increased.

Sequence analysis of mouse muscle-type phosphofructokinase gene introns 10 and 11 with special reference to the exon skipping.

To elucidate physiological relevance of the skipping of exon 11 in muscle-type phosphofructokinase (PFK-M) transcripts, we partially cloned and analyzed the cDNA and the genomic fragment of mouse PFK-M. In RT-PCR analysis using a pair of primers which carry the region corresponding to human exon 11 in between, any minor transcript without exon 11 was not detected. Partial sequencing analysis of mouse PFK-M gene revealed that the junctions of intron 10 of human gene were both less identical to the consensus sequences than those of mouse gene, but that there was no appreciable difference in the junctions in intron 11 between mouse and human.

Identification of cis-regulatory elements and trans-acting proteins of the rat carbohydrate response element binding protein gene.

Carbohydrate response element binding protein (ChREBP) is a transcription factor that activates liver glycolytic and lipogenetic enzyme genes in response to high carbohydrate diet. Here we report the transcriptional regulatory mechanisms for the rat ChREBP gene. Firstly, we determined the transcription initiation site and the nucleotide sequences of the rat ChREBP promoter region encompassing approximately 900bp from the ATG initiation codon.

Molecular cloning, expression and chromosomal localization of mouse MM-1.

The protooncogene product Myc associates with many proteins. The isolation of the mouse MM-1; c-Myc binding protein (Myc-Modulator 1) cDNA is described. The cDNA contains a 462 bp open reading frame that encodes a polypeptide of 154 amino acid residues.

Nuclear factor 1 family members interact with hepatocyte nuclear factor 1alpha to synergistically activate L-type pyruvate kinase gene transcription.

Transcription of hepatic L-type pyruvate kinase (L-PK) gene is cell type-specific and is under the control of various nutritional conditions. The L-PK gene contains multiple cis-regulatory elements located within a 170-bp upstream region necessary for these regulations. These elements can synergistically stimulate L-PK gene transcription, although their mechanisms are largely unknown.

Hex stimulates the hepatocyte nuclear factor 1alpha-mediated activation of transcription.

The homeodomain protein Hex can function either as a transcriptional repressor or activator in animals. Recent reports have indicated that Hex is involved in liver development. However, its target genes and interacting proteins are largely unknown.

Identification and characterization of the hematopoietic cell-specific enhancer-like element of the mouse hex gene.

Hex is one of the homeobox genes suggested to be important for hematopoietic cell differentiation. However, its biological function and mechanism of transcriptional regulation in hematopoietic cells remain elusive. We have identified the regulatory region necessary for transcription of the mouse Hex gene in K562 leukemia cells through transient reporter assays involving various deletion mutants.

Identification of the transactivating region of the homeodomain protein, hex.

The homeodomain-containing protein Hex acts as an activator as well as a repressor of transcription in animals. While its repression domain has been mapped to the amino-terminal region, the activation domain has never been identified. Here, we show that the homeodomain and the acidic carboxyl-terminal region are necessary for full activation of the sodium-dependent bile acid cotransporter gene promoter in a cell type-independent manner, suggesting that the carboxyl-terminal region comprising residues 197 to 271 functions as the activation domain.

Insulin stimulates expression of the pyruvate kinase M gene in 3T3-L1 adipocytes.

M2-type pyruvate kinase (M2-PK) mRNA is produced from the PKM gene by an alternative RNA splicing in adipocytes. We found that insulin increased the level of M2-PK mRNA in 3T3-L1 adipocytes in both time- and dose-dependent manners. This induction did not require the presence of glucose or glucosamine in the medium.

Insulin induces the expression of the SHARP-2/Stra13/DEC1 gene via a phosphoinositide 3-kinase pathway.

Transcription of the rat fatty acid synthase (FAS) gene in the rat liver can be regulated by feeding a high carbohydrate diet. A carbohydrate response element (ChoRE) located on the rat FAS gene promoter has been identified. Using multiple copies of the ChoRE as the bait in a yeast one-hybrid system, a rat liver cDNA library was screened, and the cDNA of ChoRE-binding proteins was cloned.