Cloning, genomic organization, expression, and effect on β-casein promoter activity of a novel isoform of the mouse Oct-1 transcription factor

Zhao, Feng‐Qi; Zheng, Yucai; Dong, Bing; Oka, Takami

doi:10.1016/j.gene.2003.10.023

Cited by 30 publications

(36 citation statements)

References 35 publications

(59 reference statements)

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“…At least four (multiple) alternatively spliced isoforms of Oct1 have been identified in mice (Zhao et al, 2004). These isoforms have a unique 3Ј terminus and a common 5Ј moiety with an intact POU binding domain.…”

Section: Inactivation Of the Mouse Oct1 Genementioning

confidence: 99%

Oct1 regulates trophoblast development during early mouse embryogenesis

et al. 2010

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SUMMARYOct1 (Pou2f1) is a transcription factor of the POU-homeodomain family that is unique in being ubiquitously expressed in both embryonic and adult mouse tissues. Although its expression profile suggests a crucial role in multiple regions of the developing organism, the only essential function demonstrated so far has been the regulation of cellular response to oxidative and metabolic stress. Here, we describe a loss-of-function mouse model for Oct1 that causes early embryonic lethality, with Oct1-null embryos failing to develop beyond the early streak stage. Molecular and morphological analyses of Oct1 mutant embryos revealed a failure in the establishment of a normal maternal-embryonic interface due to reduced extra-embryonic ectoderm formation and lack of the ectoplacental cone. Oct1 -/-blastocysts display proper segregation of trophectoderm and inner cell mass lineages. However, Oct1 loss is not compatible with trophoblast stem cell derivation. Importantly, the early gastrulation defect caused by Oct1 disruption can be rescued in a tetraploid complementation assay. Oct1 is therefore primarily required for the maintenance and differentiation of the trophoblast stem cell compartment during early post-implantation development. We present evidence that Cdx2, which is expressed at high levels in trophoblast stem cells, is a direct transcriptional target of Oct1. Our data also suggest that Oct1 is required in the embryo proper from late gastrulation stages onwards.

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Section: Inactivation Of the Mouse Oct1 Genementioning

confidence: 99%

Oct1 regulates trophoblast development during early mouse embryogenesis

et al. 2010

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“…While Runx2 has largely been regarded as a bone-specific transcription factor, it is also expressed in mammary epithelial cells (3,4,25,45,53,54). Oct-1 is also expressed in mammary epithelial cells and has been implicated in the regulation of the mammary gland-specific gene ␤-casein (21,69,70). The ␤-casein gene is an established paradigm for the study of mammary gland-specific gene expression (2,9,13,14,19,34,49,63,64).…”

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confidence: 99%

“…In contrast, less is known about the molecular mechanism by which the third essential element, block C, contributes to ␤-casein expression. Block C recruits a nuclear protein complex in mammary epithelial cells, the formation of which is dependent upon an octamer consensus sequence which recruits Oct-1 (49,52,66,69,70).…”

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confidence: 99%

Oct-1 Counteracts Autoinhibition of Runx2 DNA Binding To Form a Novel Runx2/Oct-1 Complex on the Promoter of the Mammary Gland-Specific Gene β-casein

Inman

Shore

2005

Molecular and Cellular Biology

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The transcription factor Runx2 is essential for the expression of a number of bone-specific genes and is primarily considered a master regulator of bone development. Runx2 is also expressed in mammary epithelial cells, but its role in the mammary gland has not been established. Here we show that Runx2 forms a novel complex with the ubiquitous transcription factor Oct-1 to regulate the expression of the mammary glandspecific gene ␤-casein. The Runx2/Oct-1 complex forms on a Runx/octamer element which is highly conserved in casein promoters. Chromatin immunoprecipitation, RNA interference, promoter mutagenesis, and transient expression analyses were used to demonstrate that the Runx2/Oct-1 complex contributes to the transcriptional regulation of the ␤-casein gene. Analysis of the complex revealed autoinhibitory domains for DNA binding in both the N-terminal and the C-terminal regions of Runx2. Oct-1 stimulates the recruitment of Runx2 to the ␤-casein promoter by interacting with the C-terminal region of Runx2, suggesting that Oct-1 stimulates Runx2 recruitment by relieving the autoinhibition of Runx2 DNA binding. These findings demonstrate that Runx2 collaborates with Oct-1 and contributes to the expression of a mammary gland-specific gene.The transcription factor Runx2 is a master regulator of bone development, and mutations in Runx2 are found in patients with the skeletal disorder cleidocranial dysplasia (15,28,32,33,40,43,45,58). Targeted deletion of the Runx2 gene in mice has demonstrated that Runx2 is a master regulator of osteoblast differentiation and is required for chondrocyte hypertrophy (28,32,45). Runx2 is a member of the Runt domain family of transcription factors (26,27,64,65). The Runt domain is a DNA-binding domain that specifically recognizes a consensus binding site (TGT/cGGT) found in the promoters of several cell type-specific genes (5,6,26,27,41,44,60). It has also been shown to regulate transcription in collaboration with several transcriptional regulators, including core-binding factor ␤, AP-1, Ets-1, androgen receptor, glucocorticoid receptor (GR), estrogen receptor, vitamin D 3 receptor, Smads, and STATs (12,

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“…Estimates suggest that alternative splicing occurs in 40%∼60% of human genes (Mironov et al 1999;Croft et al 2000;Kan et al 2001;Lander et al 2001;Modrek et al 2001). By using different exon combinations, alterative splicing can conceivably give birth to some dual coding regions in which the same exon sequence shared between different transcripts can encode amino acids in different reading frames.Recently several specific examples of dual coding regions have been reported in the human and mouse genomes (Scorilas et al 2001;Zhao et al 2004); however, there has been no largescale study of dual coding regions in alternatively splicing genes. The importance of comprehensively characterizing such genes, especially in the human genome, is at least twofold: (1) dual coding regions generate distinct amino acid sequences in functionally related proteins, increasing genome complexity, and the systematic and precise characterization of existing dual coding regions in alternatively spliced genes can therefore lead to improvements in gene prediction and annotation; and (2) during evolution, dual coding regions must simultaneously maintain two reading frames and are therefore shaped by unusual selective forces.…”

mentioning

confidence: 99%

“…Recently several specific examples of dual coding regions have been reported in the human and mouse genomes (Scorilas et al 2001;Zhao et al 2004); however, there has been no largescale study of dual coding regions in alternatively splicing genes. The importance of comprehensively characterizing such genes, especially in the human genome, is at least twofold: (1) dual coding regions generate distinct amino acid sequences in functionally related proteins, increasing genome complexity, and the systematic and precise characterization of existing dual coding regions in alternatively spliced genes can therefore lead to improvements in gene prediction and annotation; and (2) during evolution, dual coding regions must simultaneously maintain two reading frames and are therefore shaped by unusual selective forces.…”

mentioning

confidence: 99%

A genome-wide study of dual coding regions in human alternatively spliced genes

Liang

Landweber

2005

Genome Res.

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Alternative splicing is a major mechanism for gene product regulation in many multicellular organisms. By using different exon combinations, some coding regions can encode amino acids in multiple reading frames in different transcripts. Here we performed a systematic search through a set of high-quality human transcripts and show that ∼7% of alternatively spliced genes contain dual (multiple) coding regions. By using a conservative criterion, we found that in these regions most secondary reading frames evolved recently in mammals, and a significant proportion of them may be specific to primates. Based on the presence of in-frame stop codons in orthologous sequences in other animals, we further classified ancestral and derived reading frames in these regions. Our results indicated that ancestral reading frames are usually under stronger selection than are derived reading frames. Ancestral reading frames mainly influence the coding properties of these dual coding regions. Compared with coding regions of the whole genome, ancestral reading frames largely maintain similar nucleotide composition at each codon position and amino acid usage, while derived reading frames are significantly different. Our results also indicated that prior to acquisition of a new reading frame, the suppression of in-frame stop codons in the ancestral state is mainly achieved by one-step transition substitutions at the first or second codon position. Finally, the selective forces imposed on these dual coding regions will also be discussed.[Supplemental material is available online at www.genome.org.]Alternative splicing is a major mechanism for functional regulation in many multicellular organisms, and it plays an important role in increasing the diversity of protein products from an individual gene locus. Estimates suggest that alternative splicing occurs in 40%∼60% of human genes (Mironov et al. 1999;Croft et al. 2000;Kan et al. 2001;Lander et al. 2001;Modrek et al. 2001). By using different exon combinations, alterative splicing can conceivably give birth to some dual coding regions in which the same exon sequence shared between different transcripts can encode amino acids in different reading frames.Recently several specific examples of dual coding regions have been reported in the human and mouse genomes (Scorilas et al. 2001;Zhao et al. 2004); however, there has been no largescale study of dual coding regions in alternatively splicing genes. The importance of comprehensively characterizing such genes, especially in the human genome, is at least twofold: (1) dual coding regions generate distinct amino acid sequences in functionally related proteins, increasing genome complexity, and the systematic and precise characterization of existing dual coding regions in alternatively spliced genes can therefore lead to improvements in gene prediction and annotation; and (2) during evolution, dual coding regions must simultaneously maintain two reading frames and are therefore shaped by unusual selective forces. Thus they provide a special opport...

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Cloning, genomic organization, expression, and effect on β-casein promoter activity of a novel isoform of the mouse Oct-1 transcription factor

Cited by 30 publications

References 35 publications

Oct1 regulates trophoblast development during early mouse embryogenesis

Oct1 regulates trophoblast development during early mouse embryogenesis

Oct-1 Counteracts Autoinhibition of Runx2 DNA Binding To Form a Novel Runx2/Oct-1 Complex on the Promoter of the Mammary Gland-Specific Gene β-casein

A genome-wide study of dual coding regions in human alternatively spliced genes

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