NCBI Summary:
The protein encoded by this gene is a member of the three-amino acid loop extension (TALE) superclass of atypical homeodomains. TALE homeobox proteins are highly conserved transcription regulators. This particular homeodomain binds to a previously characterized retinoid X receptor responsive element from the cellular retinol-binding protein II promoter. In addition to its role in inhibiting 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element, the protein is an active transcriptional co-repressor of SMAD2 and may participate in the transmission of nuclear signals during development and in the adult. Mutations in this gene are associated with holoprosencephaly type 4, which is a structural anomaly of the brain. Alternative splicing has been observed at this locus and multiple splice variants encoding distinct isoforms are described. [provided by RefSeq, Jul 2013]
General function
Nucleic acid binding, DNA binding, Transcription factor
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Steroid metabolism
Comment
The homeobox gene, TGIF1, is required for chicken ovarian cortical development and generation of the juxtacortical medulla. Estermann MA et al. (2021) During early embryogenesis in amniotic vertebrates, the gonads differentiate into either ovaries or testes. The first cell lineage to differentiate gives rise to the supporting cells; Sertoli cells in males and pre-granulosa cells in females. These key cell types direct the differentiation of the other cell types in the gonad, including steroidogenic cells. The gonadal surface epithelium and the interstitial cell populations are less well studied, and little is known about their sexual differentiation programs. Here, we show the requirement of the homeobox transcription factor gene TGIF1 for ovarian development in the chicken embryo. TGIF1 is expressed in the two principal ovarian somatic cell populations, the cortex and the pre-granulosa cells of the medulla. TGIF1 expression is associated with an ovarian phenotype in estrogen-mediated sex reversal experiments. Targeted mis-expression and gene knockdown indicate that TGIF1 is required, but not sufficient, for proper ovarian cortex formation. In addition, TGIF1 is identified as the first known regulator of juxtacortical medulla development. These findings provide new insights into chicken ovarian differentiation and development, specifically cortical and juxtacortical medulla formation.//////////////////Effects of TG interaction factor 1 on synthesis of estradiol and progesterone in granulosa cells of goats through SMAD2/3-SP1 signaling pathway. An X et al. (2021) The TG interaction factor 1 (TGIF1) is of the TALE homologue domain protein family and is considered as a transcriptional repressor of SMAD protein that interacts with DNA through a specific consensus-binding site for TG and recruits mSin3A and histone deacetylases to the SMAD complex. In this study, there is the first detailed description of TGIF1 on steroidogenesis in goat granulosa cells. When there is a relatively greater expression of the TGIF1 gene, there is a lesser abundance of CYP11A1, CYP19A1, and StAR mRNA transcript and protein and 3β-HSD mRNA transcript in granulosa cells of goats. Furthermore, there were lesser concentrations of 17β-estradiol (E2) and progesterone (P4) in culture medium when there was greater TGIF1 gene expression and there were greater concentrations of these hormones in the culture medium when there was lesser TGIF1 gene expression. There may be functions of TGIF1, therefore, in suppression of SMAD-induced E2 and P4 production and in decreasing the phosphorylation of SMAD2/3 in granulosa cells of goats and relative abundance of the SMAD2/3 protein transcription factor, SP1. With suppression of TGIF1 gene expression, there was a reversal of SP1-induced suppression of steroidogenesis-related genes. Results of the present study provide insights about the potential mechanism underlying the regulation of granulosa cell steroidogenesis of goats by TGIF1.//////////////////
Expression regulated by
LH
Comment
xyz
Ovarian localization
Granulosa, Theca
Comment
Regulation of Sterol Regulatory Element Binding Transcription Factor 1a by Human Chorionic Gonadotropin and Insulin in Cultured Rat Theca-Interstitial Cells. Palaniappan M et al. Theca-interstitial (T-I) cells of the ovary synthesize androgens in response to luteinizing hormone (LH). In pathological conditions such as polycystic ovarian syndrome (PCOS), the T-I cells are hyperactive in androgen production in response to LH and insulin. Since cholesterol is an essential substrate for androgen production, we examined the effect of human chorionic gonadotropin (hCG) and insulin on signaling pathways that are known to increase cholesterol accumulation in steroidogenic cells. Specifically, the effect of hCG and insulin on sterol regulatory element binding transcription factor 1a (SREBF1a) required for cholesterol biosynthesis and uptake was examined. Primary cultures of T-I cells isolated from 25 day-old rat ovaries responded to hCG and insulin to increase the active/processed form of SREBF1a. HCG and insulin significantly reduced insulin induced gene 1 (INSIG1) protein, a negative regulator of SREBF processing. Furthermore, an increase in the expression of selected SREBF target genes, 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr) and mevalonate kinase (Mvk) was also observed. Protein kinase A (PRKA) inhibitor completely abolished the hCG-induced increase in SREBF1a while increasing INSIG1. While the hCG-induced depletion of total and free cholesterol was abolished by aminoglutethimide (AGM), the stimulatory effect on SREBF1a was not totally suppressed. Treatment with 25-hydroxycholesterol (25-OHC) abrogated the hCG effect on SREBF1a. Inhibition of the phosphatidylinositol 3-kinase pathway did not block the insulin-induced increase in SREBF1a, whereas MAP kinase inhibition reduced the insulin response. These results suggest that the increased androgen biosynthesis by the T-I cells in response to hCG and insulin, at least in part, is regulated by increasing the expression of SRE responsive genes by increasing SREBF1a.