NCBI Summary:
This gene encodes a member of the inhibitor of DNA binding (ID) protein family. These proteins are basic helix-loop-helix transcription factors which can act as tumor suppressors but lack DNA binding activity. Consequently, the activity of the encoded protein depends on the protein binding partner. [provided by RefSeq, Dec 2011]
General function
Transcription factor
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Cellular localization
Nuclear
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Ovarian function
Germ cell development
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Expression regulated by
Growth Factors/ cytokines
Comment
Inhibitor of Differentiation (Id) Genes Are Expressed in the Steroidogenic Cells of the Ovine Ovary and Are Differentially Regulated by Members of the Transforming Growth Factor-{beta} Family. Hogg K et al. Inhibitor of differentiation (Id) proteins act during embryogenesis and development to repress gene transcription required for lineage commitment, while promoting cell growth. Growth factors belonging to the TGFbeta superfamily of signaling molecules, notably the bone morphogenetic proteins (BMPs) and activin, can regulate Id expression in these tissues. Id expression and function in adult physiology is less well determined, and we hypothesized a role for Id proteins in the adult mammalian ovary. Immunohistochemistry for Id1, Id2, Id3, and Id4 in the sheep ovary revealed consistent expression in granulosa and thecal cells of ovarian follicles throughout development. In atretic follicles, Id proteins were selectively down-regulated in thecal cells (P < 0.0001). Additionally, Id1 was universally up-regulated in the cumulus cells adjacent to the oocyte. Immunohistochemistry for phospho (p)-smad 1/5/8 signaling components (stimulated by BMPs) showed a punctate pattern of expression whereas p-smad 2/3 (stimulated by activin) was ubiquitously expressed in follicles. Neither pathway, however, displayed differential staining in line with Id1 cumulus-specific expression, suggesting a more complex relationship between Id1 expression and TGFbeta signaling in these cells. Nevertheless, in vitro, stimulation of ovine granulosa cells with BMP6 or activin A led to a respective increase and decrease in Id1 (P < 0.0001), Id2 (P < 0.0001), Id3 (P < 0.0001), and Id4 (P < 0.05) transcripts, and Id1 gene expression was further manipulated by the oocyte-secreted factors BMP15 and growth differentiation factor 9 (P < 0.001). These data confirm that TGFbeta signaling can regulate Id gene expression in the sheep ovarian follicle and suggest a functional role for the Id family in the mammalian ovary.
Expression and localization of Inhibitor of Differentiation (ID) proteins during tissue and vascular remodelling in the human corpus luteum. Nio-Kobayashi J et al. Members of the transforming growth factor-?(TGF-? superfamily are likely to have major roles the regulation of tissue and vascular remodelling in the corpus luteum. There are four Inhibitor of Differentiation (ID1-4) genes that are regulated by members of the TGF-?superfamily and are involved in the transcriptional regulation of cell growth and differentiation. We studied their expression, localisation and regulation in dated human corpora lutea from across the luteal phase (n=22) and after human chorionic gonadotrophin (hCG) administration in vivo (n=5), and in luteinised granulosa cells (LGCs), using immunohistochemistry and quantitative RT-PCR. ID1-4 can be localised to multiple cell types in the corpus luteum across the luteal phase. Endothelial cell ID3 (P<0.05) and ID4 (P<0.05) immunostaining intensities peak at the time of angiogenesis but overall ID1 (P<0.05) and ID3 (P<0.05) expression peaks at the time of luteolysis and luteal ID3 expression is inhibited by hCG in vivo (P<0.01). In LGC cultures in vitro, hCG had no effect on ID1, down-regulated ID3 (P<0.001), and up-regulated ID2 (P<0.001) and ID4 (P<0.01). Bone morphogenic proteins (BMPs) had no effect on ID4 expression but up-regulated ID1 (P<0.01-P<0.005). BMP up-regulation of ID2 (P<0.05) was additive to the hCG upregulation of ID2 expression (P<0.001), while BMP cancelled out the down regulative effect of hCG on ID3 regulation. As well as documenting regulation patterns specific for ID1, ID2, ID3 and ID4, we have shown that IDs are located and differentially regulated in the human corpus luteum, suggesting a role in the transcriptional regulation of luteal cells during tissue and vascular remodelling.
Global gene expression analysis in fetal mouse ovaries
with and without meiosis and comparison of selected genes with meiosis in the testis. Olesen C et al. In order to identify novel genes involved in early meiosis and early ovarian development in the mouse, we used microarray technology to compare transcriptional activity in ovaries without meiotic germ cells at embryonic age 11.5 (E11.5) and E13.5 ovaries with meiosis. Overall, 182 genes were differentially expressed; 134 were known genes and 48 were functionally uncharacterized. A comparison of our data with the literature associated, for the first time, at least eight of the known genes with female meiosis/germ cell differentiation (Aldh1a1, C2pa, Tex12, Stk31, Lig3, Id4, Recql, Piwil2). These genes had previously only been described in spermatogenesis. The microarray also detected an abundance of vesicle-related genes of which four were upregulated (Syngr2, Stxbp1, Ric-8, SytIX) and one (Myo1c) was downregulated in E13.5 ovaries. Detailed analysis showed that the temporal expression of SytIX also coincided with the first meiotic wave in the pubertal testis. This is the first time that SytIX has been reported in non-neuronal tissue. Finally, we examined the expression of one of the uncharacterized genes and found it to be gonad-specific in adulthood. We named this novel transcript 'Gonad-expressed transcript 1' (Get-1). In situ hybridization showed that Get-1 was expressed in meiotic germ cells in both fetal ovaries and mature testis. Get-1 is therefore a novel gene in both male and female meiosis.
Follicle stages
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Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: subfertile Comment: Dual roles for Id4 in the regulation of estrogen signaling in the mammary gland and ovary. Best SA 2014 et al.
The HLH transcriptional regulator Id4 exerts important roles in different organs, including the neural compartment, where Id4 loss usually results in early lethality. To explore the role of this basally restricted transcription factor in the mammary gland, we generated a cre-inducible mouse model. MMTV- or K14-cre-mediated deletion of Id4 led to a delay in ductal morphogenesis, consistent with previous findings using a germ-line knockout mouse model. A striking increase in the expression of ERa (Esr1), PR and FoxA1 was observed in both the basal and luminal cellular subsets of Id4-deficient mammary glands. Together with chromatin immunoprecipitation of Id4 on the Esr1 and Foxa1 promoter regions, these data imply that Id4 is a negative regulator of the ERa signaling axis. Unexpectedly, examination of the ovaries of targeted mice revealed significantly increased numbers of secondary and antral follicles, and reduced Id4 expression in the granulosa cells. Moreover, expression of the cascade of enzymes that are crucial for estrogen biosynthesis in the ovary was decreased in Id4-deficient females and uterine weights were considerably lower, indicating impaired estrogen production. Thus, compromised ovarian function and decreased circulating estrogen likely contribute to the mammary ductal defects evident in Id4-deficient mice. Collectively, these data identify Id4 as a novel regulator of estrogen signaling, where Id4 restrains ERa expression in the basal and luminal cellular compartments of the mammary gland and regulates estrogen biosynthesis in the ovary.
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