DNA Methylation Profiles of Donor Nuclei Cells and Tissues of Cloned Bovine Fetuses

Kremenskoy, Maksym; Kremenska, Yuliya; Suzuki, Masako; Imai, Kyoichi; Takahashi, Seiya; Hashizume, Kazuyoshi; Yagi, Shusuke; Shiota, Kunio

doi:10.1262/jrd.17098

Cited by 36 publications

(27 citation statements)

References 42 publications

(43 reference statements)

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“…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. Cattle generated by somatic cell nuclear transfer demonstrate various abnormalities, including placental malformation, which are thought to be caused by aberrant epigenetic regulation , Hall et al 2005, Arnold et al 2006b, Rybouchkin et al 2006, and suggests that trophoblast cell differentiation is under the control of epigenetic regulation as well.…”

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

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106

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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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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

Self Cite

106

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“…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.…”

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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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“…In female mice, skewed X-inactivation is observed [114], and bovine fetuses of nuclear transfer (NT) clones show epigenetic signatures of the donor nucleus [115]. These data suggest errors or inevitable defects in DNA methylation profiles in NT cloned animals.…”

Section: Can the Epigenome Be Reset Artificially?mentioning

confidence: 98%

DNA Methylation Profile: A Composer-, Conductor-, and Player-Orchestrated Mammalian Genome Consisting of Genes and Transposable Genetic Elements

Yagi

Hirosawa

Shiota

2012

Journal of Reproduction and Development

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Abstract. Epigenetic systems play crucial roles in the differentiation of a mammalian fertilized egg into hundreds of cell types exhibiting distinct phenotypes, using a set of DNA molecules comprising about 3 billion nucleotides. Genomewide analyses of epigenetic marks have revealed the remarkably well-established and well-maintained structure of the epigenome, consisting of DNA methylation and histone modifications that vary their state in a tissue type-and developmental stage-specific manner at numerous genomic loci. DNA methylation profiles comprising numerous tissuedependent and differentially methylated regions (T-DMRs), found at such loci, are unique to every type of cell and tissue, and illuminate molecular networks that represent their phenotypes. T-DMRs are located in not only genic but also nongenic regions-including transposable genetic elements, such as short interspersed transposable element. Epigenetic studies indicate that the molecules that perform these modifications directly, such as DNA methyltransferases and eukaryotic histone methyltransferases, or indirectly, such as CpG-binding protein and noncoding RNAs-and combinations of these-contribute to the DNA methylation profile. It remains to be addressed how these molecules precisely find their target genomic loci. Key words: CpG island, DNA methylation profile, Methylome, Tissue-dependent and differently methylated region (T-DMR) (J. Reprod. Dev. 58: [265][266][267][268][269][270][271][272][273] 2012) T he mammalian body consists of about 200 types of cells, which can be discriminated from each other by their phenotype. All cells are descendants of a single fertilized egg. During development, cells change their phenotypes and their fates by responding to extrinsic and intrinsic signals using appropriate, but distinct, sets of genes without changing the genome sequence. Sets of transcription factors are the major players that govern the cell type-and tissue-specific use of the genome. Recent studies indicate that expression of these key players is under the control of another mechanism [1, 2]-the epigenetic system-that enables cells to exhibit their stable cell type-specific phenotypes over multiple generations. The epigenetic system, therefore, is considered a memory for genome use that defines cell types and tissues.The epigenome is the genome-wide combination of DNA methylation, histone modifications, and chromatin architecture. Recent advances in technology allow us to analyze the epigenome comprehensively. In this review, we would like to elucidate the mammalian epigenome by profiling T-DMRs, and to address the relationship between the epigenome and the genome. DNA Methylation is a Major Player in the Epigenetic SystemThe major components of the epigenetic system are DNA methylation and histone modifications. In mammals, DNA methylation occurs at the cytosine residues (C) in CpG dinucleotide sequences, and is involved in imprinting, X-inactivation, immobilization of transposable genomic elements, and the regulation of gene activity [3]. ...

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DNA Methylation Profiles of Donor Nuclei Cells and Tissues of Cloned Bovine Fetuses

Cited by 36 publications

References 42 publications

Blastocyst elongation, trophoblastic differentiation, and embryonic pattern formation

Blastocyst elongation, trophoblastic differentiation, and embryonic pattern formation

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

DNA Methylation Profile: A Composer-, Conductor-, and Player-Orchestrated Mammalian Genome Consisting of Genes and Transposable Genetic Elements

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