The GC box is a common regulatory DNA element of eukaryotic genes. The promoter region of
rat CYP1A1 contains a single GC box within a basic transcriptional element (BTE)
required for constitutive expression of the gene. By screening a liver library for the ability to bind
BTE, Imataka et al. (1992) isolated rat cDNAs encoding Sp1 and a protein that they
designated BTEB (BTE binding protein). Sequence analysis revealed that, like Sp1, BTEB
contains 3 consecutive zinc finger motifs. In transient transfection experiments both BTEB and
Sp1 stimulated promoters with repeated GC boxes.
NCBI Summary:
The protein encoded by this gene is a transcription factor that binds to GC box elements located in the promoter. Binding of the encoded protein to a single GC box inhibits mRNA expression while binding to tandemly repeated GC box elements activates transcription. [provided by RefSeq, Jul 2008]
General function
Nucleic acid binding, DNA binding, Transcription factor
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Preantral follicle growth, Steroid metabolism
Comment
Spatio-Temporal Gene Expression Profiling during In Vivo Early Ovarian Folliculogenesis: Integrated Transcriptomic Study and Molecular Signature of Early Follicular Growth. Bonnet A et al. (2015) The successful achievement of early ovarian folliculogenesis is important for fertility and reproductive life span. This complex biological process requires the appropriate expression of numerous genes at each developmental stage, in each follicular compartment. Relatively little is known at present about the molecular mechanisms that drive this process, and most gene expression studies have been performed in rodents and without considering the different follicular compartments. We used RNA-seq technology to explore the sheep transcriptome during early ovarian follicular development in the two main compartments: oocytes and granulosa cells. We documented the differential expression of 3,015 genes during this phase and described the gene expression dynamic specific to these compartments. We showed that important steps occurred during primary/secondary transition in sheep. We also described the in vivo molecular course of a number of pathways. In oocytes, these pathways documented the chronology of the acquisition of meiotic competence, migration and cellular organization, while in granulosa cells they concerned adhesion, the formation of cytoplasmic projections and steroid synthesis. This study proposes the involvement in this process of several members of the integrin and BMP families. The expression of genes such as Kruppel-like factor 9 (KLF9) and BMP binding endothelial regulator (BMPER) was highlighted for the first time during early follicular development, and their proteins were also predicted to be involved in gene regulation. Finally, we selected a data set of 24 biomarkers that enabled the discrimination of early follicular stages and thus offer a molecular signature of early follicular growth. This set of biomarkers includes known genes such as SPO11 meiotic protein covalently bound to DSB (SPO11), bone morphogenetic protein 15 (BMP15) and WEE1 homolog 2 (S. pombe)(WEE2) which play critical roles in follicular development but other biomarkers are also likely to play significant roles in this process. To our knowledge, this is the first in vivo spatio-temporal exploration of transcriptomes derived from early follicles in sheep.//////////////////
Expression regulated by
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Ovarian localization
Granulosa
Comment
Regulation of Kruppel-like factor 4, 9 and 13 genes and the steroidogenic genes LDLR, StAR and CYP11A in ovarian granulosa cells. Natesampillai S et al. Kruppel-like factors (KLF's) are important Sp1-like eukaryotic transcriptional proteins. The LDLR, StAR and CYP11A genes exhibit GC-rich Sp1-like sites, which have the potential to bind KLF's in multiprotein complexes. We now report that KLF4, KLF9 and KLF13 transcripts are expressed in and regulate ovarian cells. KLF4 and 13, but not KLF9, mRNA expression was induced and then repressed over time (P < 0.001). Combined LH and IGF-I stimulation increased KLF4 mRNA at 2 h (P < 0.01), whereas LH decreased KLF13 mRNA at 6 h (P < 0.05) and IGF-I reduced KLF13 at 24 h (P < 0.01) compared with untreated control. KLF9 was not regulated by either hormone. Transient transfection of KLF4, KLF9 and KLF13 suppressed LDLR/luc, StAR/luc and CYP11A/luc by 80 to 90% (P < 0.001). Histone-deacetylase (HDAC) inhibitors stimulated LDLR/luc by 5-6 fold and StAR/luc and CYP11A/luc activity by 2-fold (P < 0.001), and partially reversed suppression by all 3 KLF's (P < 0.001). Deletion of the zinc-finger domain of KLF13 abrogated repression of LDLR/luc. Lentiviral overexpression of the KLF13 gene suppressed LDLR mRNA (P < 0.001) and CYP11A mRNA (P = 0.003), but increased StAR mRNA (P = 0.007). Collectively, these data suggest that KLF's may recruit inhibitory complexes containing HDAC corepressors, thereby repressing LDLR and CYP11A transcription. Conversely, KLF13 may recruit unknown coactivators or stabilize StAR mRNA, thereby explaining enhancement of in situ StAR gene expression. These data introduce new potent gonadal transregulators of genes encoding proteins that mediate sterol uptake and steroid biosynthesis. Key words: KLF4, KLF9, KLF13, LDLR, StAR.