Identification of Novel First Exons in Ad4BP/SF-1 (NR5A1) Gene and Their Tissue- and Species-Specific Usage

Kimura, Ryota; Yoshii, Hironori; Nomura, Masatoshi; Kotomura, Naoe; Mukai, Tokuo; Ishihara, Satoru; Ohba, Koichi; Yanase, Toshihiko; Gotoh, Osamu; Nawata, Hajime; Morohashi, Ken Ichirou

doi:10.1006/bbrc.2000.3774

Cited by 24 publications

(14 citation statements)

References 37 publications

(32 reference statements)

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“…This is similar to a published EST (AK097060) where E1c is present but connected to E3. For these specific GATA4 transcripts, the combination of poor conservation and low level of expression render the biological significance of these transcripts unlikely, as suggested for the Nr5a1/Sf1 gene [42]. In contrast, E1b was not only well conserved between rodents and human from a sequence standpoint, but was also expressed at significant levels in most, if not all, GATA4-expressing tissues examined (Figures 3A and 4A).…”

Section: Discussionmentioning

confidence: 86%

Conserved Usage of Alternative 5′ Untranslated Exons of the GATA4 Gene

et al. 2009

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BackgroundGATA4 is an essential transcription factor required for the development and function of multiple organs. Despite this important role, our knowledge of how the GATA4 gene is regulated remains limited. To better understand this regulation, we characterized the 5′ region of the mouse, rat, and human GATA4 genes.Methodology/Principal FindingsUsing 5′ RACE, we identified novel transcription start sites in all three species. GATA4 is expressed as multiple transcripts with varying 5′ ends encoded by alternative untranslated first exons. Two of these non-coding first exons are conserved between species: exon 1a located 3.5 kb upstream of the GATA4 ATG site in exon 2, and a second first exon (exon 1b) located 28 kb further upstream. Expression of both mRNA variants was found in all GATA4-expressing organs but with a preference for the exon 1a–containing transcript. The exception was the testis where exon 1a– and 1b–containing transcripts were similarly expressed. In some tissues such as the intestine, alternative transcript expression appears to be regionally regulated. Polysome analysis suggests that both mRNA variants contribute to GATA4 protein synthesis.Conclusions/SignificanceTaken together, our results indicate that the GATA4 gene closely resembles the other GATA family members in terms of gene structure where alternative first exon usage appears to be an important mechanism for regulating its tissue- and cell-specific expression.

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Section: Discussionmentioning

confidence: 86%

Conserved Usage of Alternative 5′ Untranslated Exons of the GATA4 Gene

et al. 2009

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“…The Ad4BP/SF-1 gene has multiple noncoding first exons (Ia, Ig, and Ix), and exon usage is differentially regulated among tissues (28). Therefore, we examined the transcriptional activity of a 5.8-kb DNA fragment upstream of exon 2.…”

Section: Resultsmentioning

confidence: 99%

Two-Step Regulation of Ad4BP/SF-1 Gene Transcription during Fetal Adrenal Development: Initiation by a Hox-Pbx1-Prep1 Complex and Maintenance via Autoregulation by Ad4BP/SF-1

Zubair

Ishihara

Oka

et al. 2006

Molecular and Cellular Biology

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The orphan nuclear receptor Ad4BP/SF-1 (adrenal 4 binding protein/steroidogenic factor 1) is essential for the proper development and function of reproductive and steroidogenic tissues. Although the expression of Ad4BP/SF-1 is specific for those tissues, the mechanisms underlying this tissue-specific expression remain unknown. In this study, we used transgenic mouse assays to examine the regulation of the tissue-specific expression of Ad4BP/SF-1. An investigation of the entire Ad4BP/SF-1 gene locus revealed a fetal adrenal enhancer (FAdE) in intron 4 containing highly conserved binding sites for Pbx-Prep, Pbx-Hox, and Ad4BP/ SF-1. Transgenic assays revealed that the Ad4 sites, together with Ad4BP/SF-1, develop an autoregulatory loop and thereby maintain transcription, while the Pbx/Prep and Pbx/Hox sites initiate transcription prior to the establishment of the autoregulatory loop. Indeed, a limited number of Hox family members were found to be expressed in the adrenal primordia. Whether a true fetal-type adrenal cortex is present in mice remained controversial, and this argument was complicated by the postnatal development of the so-called X zone. Using transgenic mice with lacZ driven by the FAdE, we clearly identified a fetal adrenal cortex in mice, and the X zone is the fetal adrenal cells accumulated at the juxtamedullary region after birth.

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“…These data combined show that different NFAT C-termini could potentially have functionally unique characteristics, emphasizing that although NFAT proteins may have redundancy in their functions, as can be concluded from knockout studies [47,48], the specific functions of different NFAT isoforms could have an impact on Ca 2+ -dependent gene expression in different tissues and species depending on the isoform expressed. Species-specific splicing and usage of alternative 5′ exons have also been shown to regulate other genes, for example, splicing of the p53 tumor suppressor gene [49] and usage of 5′ exons of the transcription factor NR5A1 [50].…”

Section: Discussionmentioning

confidence: 99%

Alternative splicing and expression of human and mouse NFAT genes

2008

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Four members of the nuclear factor of activated T cells (NFAT) family (NFATC1, NFATC2, NFATC3, and NFATC4) are Ca2+-regulated transcription factors that regulate several processes in vertebrates, including the development and function of the immune, cardiovascular, musculoskeletal, and nervous systems. Here we describe the structures and alternative splicing of the human and mouse NFAT genes, including novel splice variants for NFATC1, NFATC2, NFATC3, and NFATC4, and show the expression of different NFAT mRNAs in various mouse and human tissues and brain regions by RT-PCR. Our results show that alternatively spliced NFAT mRNAs are expressed differentially and could contribute to the diversity of functions of the NFAT proteins. Since NFAT family members are Ca2+-regulated and have critical roles in neuronal gene transcription in response to electrical activity, we describe the expression of NFATC1, NFATC2, NFATC3, and NFATC4 mRNAs in the adult mouse brain and in the adult human hippocampus using in situ hybridization and show that all NFAT mRNAs are expressed in the neurons of the mouse brain with specific patterns for each NFAT.

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Identification of Novel First Exons in Ad4BP/SF-1 (NR5A1) Gene and Their Tissue- and Species-Specific Usage

Cited by 24 publications

References 37 publications

Conserved Usage of Alternative 5′ Untranslated Exons of the GATA4 Gene

Conserved Usage of Alternative 5′ Untranslated Exons of the GATA4 Gene

Two-Step Regulation of Ad4BP/SF-1 Gene Transcription during Fetal Adrenal Development: Initiation by a Hox-Pbx1-Prep1 Complex and Maintenance via Autoregulation by Ad4BP/SF-1

Alternative splicing and expression of human and mouse NFAT genes

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