DNA Methylation-dependent Epigenetic Regulation of Dimethylarginine Dimethylaminohydrolase 2 Gene in Trophoblast Cell Lineage

Tomikawa, Junko; Fukatsu, Kazumi; Tanaka, Satoshi; Shiota, Kunio

doi:10.1074/jbc.m513782200

Cited by 50 publications

(52 citation statements)

References 37 publications

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“…Tomikawa et al previously demonstrated that methylation in this region associated with the silencing of DDAH-2 expression. 55 These results showed a similar trend with the current experiments.…”

Section: Discussionsupporting

confidence: 81%

146 Demethylation Treatment Restores Erectile Function in a Rat Model of Hyperhomocysteinemia

Zhang

Dai

2017

The Journal of Sexual Medicine

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Section: Discussionsupporting

confidence: 81%

146 Demethylation Treatment Restores Erectile Function in a Rat Model of Hyperhomocysteinemia

Zhang

Dai

2017

The Journal of Sexual Medicine

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“…Epigenetic regulation of transcription factors by DNA methylation and histone acetylation have recently been found to regulate imprinted genes, in mouse and humans, and some trophoblast related genes may also be involved in epigenetic regulation: reports suggest NANOG, POU5F1, sal-like protein 3 (SALL3), and serpin inhibitor clade B member 5 (SERPINB5) are involved in epigenetic regulation that influence trophoblast cell proliferation, differentiation, and invasion (Ohgane et al 2004, Dokras et al 2006, Ferguson-Smith et al 2006, Tomikawa et al 2006. However, in the bovine embryo, there is again only limited evidence regarding epigenetic modification of trophoblastspecific genes (Kremenskoy et al 2006a(Kremenskoy et al , 2006b.…”

Section: Roles Of Trophoblast-specific Genes From Gastrulation To Permentioning

confidence: 99%

Blastocyst elongation, trophoblastic differentiation, and embryonic pattern formation

Blomberg¹,

Hashizume²,

Viebahn³

2008

Reproduction

107

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The molecular basis of ungulate and non-rodent conceptus elongation and gastrulation remains poorly understood; however, use of stateof-the-art genomic technologies is beginning to elucidate the mechanisms regulating these complicated processes. For instance, transcriptome analysis of elongating porcine concepti indicates that protein synthesis and trafficking, cell growth and proliferation, and cellular morphology are major regulated processes. Furthermore, potential autocrine roles of estrogen and interleukin-1-b in regulating porcine conceptus growth and remodeling and metabolism have become evident. The importance of estrogen in pig is emphasized by the altered expression of essential steroidogenic and trophoblast factors in lagging ovoid concepti. In ruminants, the characteristic mononucleate trophoblast cells differentiate into a second lineage important for implantation, the binucleate trophoblast, and transcriptome profiling of bovine concepti has revealed a gene cluster associated with rapid trophoblast proliferation and differentiation. Gene cluster analysis has also provided evidence of correlated spatiotemporal expression and emphasized the significance of the bovine trophoblast cell lineage and the regulatory mechanism of trophoblast function. As a part of the gastrulation process in the mammalian conceptus, specification of the germ layers and hence definitive body axes occur in advance of primitive streak formation. Processing of the transforming growth factor-b-signaling molecules nodal and BMP4 by specific proteases is emerging as a decisive step in the initial patterning of the pre-gastrulation embryo. The topography of expression of these and other secreted molecules with reference to embryonic and extraembryonic tissues determines their local interaction potential. Their ensuing signaling leads to the specification of axial epiblast and hypoblast compartments through cellular migration and differentiation and, in particular, the specification of the early germ layer tissues in the epiblast via gene expression characteristic of endoderm and mesoderm precursor cells.

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“…Non-CpG methylation in mammals is quite rare, whereas non-CpG methylation as CNG (N can be any base) is common in plants [8], bacteria [9,10] and yeast [11]. In mammals, DNA methylation of CpGs is involved in various phenomena from development through gene silencing, splicing, stabilizing and chromatin remodeling [1,[12][13][14][15][16][17][18][19][20][21]. In contrast, the biological role of non-CpG methylation in mammals is unknown.…”

mentioning

confidence: 99%

Non-CpG Methylation Occurs in the Regulatory Region of the Sry Gene

et al. 2011

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Abstract. The Sry (sex determining region on Y chromosome) gene is a master gene for sex determination. We previously reported that the Sry gene has tissue-dependent and differentially methylated regions (T-DMRs) by analyzing the DNA methylation states at CpG sites in the promoter regions. In this study, we found unique non-CpG methylation at the internal cytosine in the 5'-CCTGG-3' pentanucleotide sequence in the Sry T-DMR. This non-CpG methylation was detected in four mouse strains (ICR, BALB/c, DBA2 and C3H), but not in two strains (C57BL/6 and 129S1), suggesting that the CCTGG methylation is tentative and unstable. Interestingly, this CCTGG methylation was associated with demethylation of the CpG sites in the Sry T-DMR in the developmental process. A methylationmediated promoter assay showed that the CCTGG methylation promotes gene expression. Our finding shows that non-CpG methylation has unique characteristic and is still conserved in mammals. Key words: DNA methylation, Non-CpG methylation, Sry (J. Reprod. Dev. 57: [586][587][588][589][590][591][592][593] 2011) NA methylation plays an important role in normal differentiation, development and cloned animals [1][2][3][4]. Eukaryotic DNA contains 5-methylcytosine as the only methylated nucleotide in the genome. The methylation of cytosine occurs mainly at the CpG site in mammals [5][6][7]. Non-CpG methylation in mammals is quite rare, whereas non-CpG methylation as CNG (N can be any base) is common in plants [8], bacteria [9,10] and yeast [11]. In mammals, DNA methylation of CpGs is involved in various phenomena from development through gene silencing, splicing, stabilizing and chromatin remodeling [1,[12][13][14][15][16][17][18][19][20][21]. In contrast, the biological role of non-CpG methylation in mammals is unknown.Sry (sex determining region on the Y chromosome) is the master gene for initiating the cascade leading to testicular differentiation in mammals [22]. Expression of the Sry gene is restricted to gonadal somatic cells at 10.5-12.5 days postcoitum (dpc) in the mouse [23][24][25]. The Sry gene produces two types of transcripts with different transcription start sites, linear and circular forms [24,26]. The linear transcript is translated into protein and is expressed only from 10.5 to 12.5 dpc in the pre-Sertoli cells in the developing male gonad [23][24][25], whereas the circular form is thought to be untranslated [23,[27][28][29]. The Sry gene has tissue-dependent and differentially methylated regions (T-DMRs), and the CpG methylation kinetics coincide with the spatio-temporal expression of the Sry gene [19]. Thus, the Sry locus may be an interesting model for acquiring the epigenetic regulation and development of the gonad from the evolutional aspect in mammals.Previous studies reported methylation at the CCWGG (W=A or T) pentanucleotide sequence in mammals [30][31][32][33], but the function of CCWGG methylation remains unknown. Here, we report on the methylation of the CCTGG pentanucleotide sequence in the Sry locus. We examined DNA methyla...

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DNA Methylation-dependent Epigenetic Regulation of Dimethylarginine Dimethylaminohydrolase 2 Gene in Trophoblast Cell Lineage

Cited by 50 publications

References 37 publications

146 Demethylation Treatment Restores Erectile Function in a Rat Model of Hyperhomocysteinemia

146 Demethylation Treatment Restores Erectile Function in a Rat Model of Hyperhomocysteinemia

Blastocyst elongation, trophoblastic differentiation, and embryonic pattern formation

Non-CpG Methylation Occurs in the Regulatory Region of the Sry Gene

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