Tetsuya Mizutani et al 2001 reported the cloning and Characterization of
Gonadotropin-Inducible Ovarian Transcription
Factors (GIOT1 and -2) That Are Novel Members of
the (Cys)2-(His)2-Type Zinc Finger Protein Family.
Gonadotropins are essential for ovarian follicular development and differentiation. To identify genes that are rapidly
induced by gonadotropin in the immature rat ovary, ovarian genes were screened by a subtraction cloning procedure.
cDNA clones encoding novel members of the (Cys)2-(His)2-type zinc finger protein family GIOT1 and -2 (gonadotropin-inducible transcription factor 1 and 2), were identified. Two isoforms of GIOT2 (GIOT2 and 2),
which are probably produced by alternative splicing, also exist. Nucleotide sequence analysis revealed that GIOT1, but
not GIOT2, contains the krppel-associated box-A domain at the NH2 terminus. RNA analyses revealed that these
mRNAs were rapidly and temporarily induced by gonadotropins in the rat testis as well as in the ovary. In situ
hybridization study revealed that expression of GIOT1 was induced in theca interna cells in the ovary and Leydig cells
in the testis. Interestingly, the gene expression of GIOT1 is restricted to the pituitary, adrenal, testis, and ovary, while
GIOT2 gene is expressed ubiquitously. A functional analysis of GIOT1 and -2 by a GAL4-based mammalian
one-hybrid system revealed that GIOT1, but not GIOT2, is a transcriptional repressor and that the krppel-associated
box-A domain of GIOT1 is responsible for the transcriptional repressor activity. A GAL4-based yeast two-hybrid
system was also used to identify proteins that interact with the rat GIOT1. The authors cloned genes encoding rat homologs of
human I-mfa domain containing protein and transcriptional intermediary factor 1 , both of which are
transcription-regulatory proteins. Interaction of these proteins with GIOT1 was directly demonstrated by GST
pull-down assay. The data strongly suggest that GIOT1 may function as a novel transcriptional repressor by working with rat homologs of human I-mfa domain containing protein and transcriptional intermediary factor 1 proteins and
may play a significant role at the transcription level in the folliculogenesis.