AP-1-Like Motif as a Key to Understanding the Insulin-Like Growth Factor I (IGF-I) Gene Regulation.

Kajimoto, Yoshitaka; Umayahara, Yutaka

doi:10.1507/endocrj.45.1

Cited by 11 publications

(9 citation statements)

References 24 publications

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“…How Fra-1 modulates genes through which the pool of active osteoblasts is expanded remains to be explained. Although it is conceivable that Fra-1 induces the expression of osteogenic growth factors or their receptors, we did not find increased expression of transforming growth factor-β1 or insulin-like growth factor I genes, which carry functional AP-1 binding sites 17,18 . Besides affecting signaling components, Fra-1 might directly increase the expression of its own osteoblast-specific target genes.…”

Section: Discussioncontrasting

confidence: 91%

Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1

Jochum

David

Elliott

et al. 2000

Nat Med

296

250

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Bone formation by osteoblasts is essential for skeletal growth and remodeling. Fra-1 is a c-Fos-related protein belonging to the AP-1 family of transcription factors. Here we show that transgenic mice overexpressing Fra-1 in various organs develop a progressive increase in bone mass leading to osteosclerosis of the entire skeleton, which is due to a cell-autonomous increase in the number of mature osteoblasts. Moreover, osteoblast differentiation, but not proliferation, was enhanced and osteoclastogenesis was also elevated in vitro. These data indicate that, unlike c-Fos, which causes osteosarcomas, Fra-1 specifically enhances bone formation, which may be exploited to stimulate bone formation in pathological conditions.

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Section: Discussioncontrasting

confidence: 91%

Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1

Jochum

David

Elliott

et al. 2000

Nat Med

296

250

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“…Previous reports have described an AP1 element in the chicken Igf1 promoter that mediates estrogen regulation (16,30). Comparison of sequences in this vicinity of the chicken and mouse promoters indicated that no homologous region is present in mammals (supplemental Fig.…”

Section: Resultsmentioning

confidence: 83%

“…Similarly, O2OS cells stably expressing the NERKI ER␣ lacked E 2 -dependent Igf1 regulation (33), and a different DNA ER␣ binding mutant also failed to increase uterine Igf1 transcript in response to E 2 (34). Comparison of the previously described AP1 element in the chicken Igf1 promoter (16,30) to mammalian sequences indicated that there was no homologous region in the mammalian Igf1 genes (supplemental Table S5 and Fig. S2).…”

Section: Discussionmentioning

confidence: 89%

Estrogen-mediated Regulation of Igf1 Transcription and Uterine Growth Involves Direct Binding of Estrogen Receptor α to Estrogen-responsive Elements

Hewitt

Yin

et al. 2010

Journal of Biological Chemistry

109

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Estrogen enables uterine proliferation, which depends on synthesis of the IGF1 growth factor. This proliferation and IGF1 synthesis requires the estrogen receptor (ER), which binds directly to target DNA sequences (estrogen-responsive elements or EREs), or interacts with other transcription factors, such as AP1, to impact transcription. We observe neither uterine growth nor an increase in Igf1 transcript in a mouse with a DNA-binding mutated ER␣ (KIKO), indicating that both Igf1 regulation and uterine proliferation require the DNA binding function of the ER. We identified several potential EREs in the Igf1 gene, and chromatin immunoprecipitation analysis revealed ER␣ binding to these EREs in wild type but not KIKO chromatin. STAT5 is also reported to regulate Igf1; uterine Stat5a transcript is increased by estradiol (E 2 ), but not in KIKO or ␣ERKO uteri, indicating ER␣-and ERE-dependent regulation. ER␣ binds to a potential Stat5a ERE. We hypothesize that E 2 increases Stat5a transcript through ERE binding; that ER␣, either alone or together with STAT5, then acts to increase Igf1 transcription; and that the resulting lack of IGF1 impairs KIKO uterine growth. Treatment with exogenous IGF1, alone or in combination with E 2 , induces proliferation in wild type but not KIKO uteri, indicating that IGF1 replacement does not rescue the KIKO proliferative response. Together, these observations suggest in contrast to previous in vitro studies of IGF-1 regulation involving AP1 motifs that direct ER␣-DNA interaction is required to increase Igf1 transcription. Additionally, full ER␣ function is needed to mediate other cellular signals of the growth factor for uterine growth.

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“…Our novel finding that estrogen upregulates c-FOS expression in monkey DLPFC neurons suggests that c-FOS is involved in estrogen-induced neuronal activation and plasticity in this structure in primates as well. Moreover, c-FOS induction may well contribute to estrogenic promotion of IGF1 expression in the DLPFC, because the AP1 complex is implicated in IGF1 gene expression (Kajimoto and Umayahara, 1998).…”

Section: Discussionmentioning

confidence: 99%

Estradiol alters transcription factor gene expression in primate prefrontal cortex

Wang

Cheng

Zhou

et al. 2004

J of Neuroscience Research

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Estrogen protects neurons from a variety of experimental insults in vitro, and is thought to protect from acute and chronic neurodegenerative processes in vivo. Estrogen also enhances higher-level cognitive functions that are centered in the dorsolateral prefrontal cortex (DLPFC) in human and non-human primates. To investigate genomic mechanisms involved in estrogenic effects on the primate brain in vivo, we compared transcription factor mRNA and protein expression in the DLPFC of ovariectomized rhesus monkeys treated with either vehicle or estradiol (E2). c-FOS, E2F1, and general transcription factor IIB (TFIIB) mRNA and protein expression were altered significantly by short-term E2 treatment, as shown by DNA array, in situ hybridization, and immunohistochemical and immunoblot evaluations. C-FOS expression was increased significantly whereas E2F1 and TFIIB levels were decreased in the DLPFC of E2-treated animals. These transcription factors were concentrated in cortical pyramids, as were estrogen receptors alpha and beta. These data indicate that estrogen may have direct as well as indirect effects on neuronal gene expression in the primate prefrontal cortex.

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AP-1-Like Motif as a Key to Understanding the Insulin-Like Growth Factor I (IGF-I) Gene Regulation.

Cited by 11 publications

References 24 publications

Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1

Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1

Estrogen-mediated Regulation of Igf1 Transcription and Uterine Growth Involves Direct Binding of Estrogen Receptor α to Estrogen-responsive Elements

Estradiol alters transcription factor gene expression in primate prefrontal cortex

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