Molecular cloning and analysis of the 5′-flanking region of the human MYPT1 gene

Machida, Hirofumi; M, Ito; Okamoto, Ryuji; Shiraki, Katsuya; Isaka, Naoki; Hartshorne, David J.; Nakano, Takeshi

doi:10.1016/s0167-4781(00)00285-2

Cited by 14 publications

(14 citation statements)

References 24 publications

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“…Deletion of SMTNL1 produces an extraordinary effect on basal expression in neonates and sexually immature mice, increasing MYPT1 over 40-fold compared with WT litter mates. Prior to this study MYPT1 has not been thought to have much capacity to be regulated at the protein level, largely due to an absence of recognized transcription factor binding sites in its promoter region (23). However, our studies examining MYPT1 mRNA levels by real time PCR in response to pregnancy support recent findings of Fischer et al (15) in uterine artery showing both an increase in MYPT1 expression at both the protein and message level, suggesting that the protein is transcriptional regulated.…”

Section: Discussionsupporting

confidence: 72%

“…MYPT1 is expressed in smooth muscles, whereas MYPT2 and 3 are expressed preferentially in heart, skeletal muscle (SKM), and brain (22). Although the MYPT promoter lacks recognizable transcription factor binding sites suggesting its expression may not be regulated, isoform switching from MYPT1 to MYPT2 was observed in the differentiation of C2C12 cells from nonmuscle to skeletal muscle cells (23,24). Additionally, developmental switch of MYPT1 isoforms caused a significant increase in the rate of relaxation in the transition from the fetal to the adult circulation in rat vascular smooth muscle (25).…”

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confidence: 99%

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Smoothelin-like 1 Protein Regulates Myosin Phosphatase-targeting Subunit 1 Expression during Sexual Development and Pregnancy*

Lontay

Bodoor

Weitzel

et al. 2010

Journal of Biological Chemistry

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Pregnancy coordinately alters the contractile properties of both vascular and uterine smooth muscles reducing systemic blood pressure and maintaining uterine relaxation. The precise molecular mechanisms underlying these pregnancy-induced adaptations have yet to be fully defined but are likely to involve changes in the expression of proteins regulating myosin phosphorylation. Here we show that smoothelin like protein 1 (SMTNL1) is a key factor governing sexual development and pregnancy induced adaptations in smooth and striated muscle. A primary target gene of SMTNL1 in these muscles is myosin phosphatase-targeting subunit 1 (MYPT1). Deletion of SMTNL1 increases expression of MYPT1 30 -40-fold in neonates and during development expression of both SMTNL1 and MYPT1 increases over 20-fold. Pregnancy also regulates SMTNL1 and MYPT1 expression, and deletion SMTNL1 greatly exaggerates expression of MYPT1 in vascular smooth muscle, producing a profound reduction in force development in response to phenylephrine as well as sensitizing the muscle to acetylcholine. We also show that MYPT1 is expressed in Type2a muscle fibers in mice and humans and its expression is regulated during pregnancy, suggesting unrecognized roles in mediating skeletal muscle plasticity in both species. Our findings define a new conserved pathway in which sexual development and pregnancy mediate smooth and striated muscle adaptations through SMTNL1 and MYPT1.

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Section: Discussionsupporting

confidence: 72%

mentioning

confidence: 99%

Smoothelin-like 1 Protein Regulates Myosin Phosphatase-targeting Subunit 1 Expression during Sexual Development and Pregnancy*

Lontay

Bodoor

Weitzel

et al. 2010

Journal of Biological Chemistry

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“…Thus one MYPT1 gene is adequate for normal expression of MYPT1. A previous analysis of the MYPT1 promoter region suggested that MYPT1 is a housekeeping gene (Machida et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

The targeted disruption of the MYPT1 gene results in embryonic lethality

Okamoto

Suzuki

et al. 2005

Transgenic Res

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Myosin phosphatase (MP) is a major phosphatase responsible for the dephosphorylation of the regulatory light chain of myosin II. MYPT1, a target subunit of smooth and nonmuscle MP, is responsible for activation and regulation of MP. To identity the physiological roles of MP, we have generated MYPT1-deficient mice by gene targeting. The heterozygous mice showed no changes in expression levels of MYPT1 and no distinct phenotype compared to wild-type mice was observed. None of the F2 mice were homozygous for the MYPT1 deletion, indicating that the targeted disruption of the MYPT1 gene resulted in embryonic lethality. The point of embryonic lethality is before 7.5 dpc. These findings indicate that MYPT1 is essential for mouse embryogenesis.

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“…Aside from the length of the promoter regions important for gene expression, base composition of the PPRs is another key element involved in the regulatory control of gene expression (Clegg et al 1996;Machida et al 2001). Clegg et al (1996) reported that the GC-rich proximal promoter is responsible for cell type-specific expression in vivo in mouse brain.…”

Section: Introductionmentioning

confidence: 99%

“…In human, myosin phosphatase target subunit 1 (MYPT1) gene is a housekeeping gene. The basal promoter activity for MYPT1 gene expression is due to a 268 bp GC-rich fragment in the 5 Kb promoter region that contained one Sp1 transcription factor binding site upstream from the transcription start site (TSS) (Machida et al 2001). However, it is not clear whether the PPRs with different lengths have different base compositions and whether base composition of the PPRs is related to the gene expression profiles in human tissues.…”

Section: Introductionmentioning

confidence: 99%

Computational analysis of base composition pattern and promoter elements in the putative promoter regions in relation to expression profiles of 682 human genes on chromosome 22

et al. 2006

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The base composition pattern (BCP) in the putative promoter region (PPRs) up to 5 Kb lengths of 682 human genes on Chromosome 22 (Chr22) was examined. Two-dimensional (2D) and three-dimensional (3D) functions were designed to delineate the DNA base composition, with four major patterns identified. It is found that 17.6% genes include TATA box, 28.0% GC box, 18.9% CAAT box and 38.4% CpG islands, and approximately 10% genes have one of four putative initiator (Inr) motifs. The occurrence of the promoter elements is tightly associated with the base composition features in the promoter regions, and the associations of the base composition features with occurrence of the promoter elements in the promoter regions mediate tissue-wide expression of the genes in human. The occurrence of two or more promoter elements in the promoter regions is required for the medium- and wide-range expression profiles of the human genes on Chr22. Thus, the reported data shed light on the characteristics of the PPRs of the human genes on Chr22, which may improve our understanding of regulatory roles of the PPRs with occurrence of the promoter elements in gene expression.

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Molecular cloning and analysis of the 5′-flanking region of the human MYPT1 gene

Cited by 14 publications

References 24 publications

Smoothelin-like 1 Protein Regulates Myosin Phosphatase-targeting Subunit 1 Expression during Sexual Development and Pregnancy*

Smoothelin-like 1 Protein Regulates Myosin Phosphatase-targeting Subunit 1 Expression during Sexual Development and Pregnancy*

The targeted disruption of the MYPT1 gene results in embryonic lethality

Computational analysis of base composition pattern and promoter elements in the putative promoter regions in relation to expression profiles of 682 human genes on chromosome 22

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