The paternal methylation imprint of the mouse <i>H19</i> locus is acquired in the gonocyte stage during foetal testis development

Ueda, Takayuki; Abe, Kuniya; Miura, Ai; Yuzuriha, Misako; Zubair, Mohamad; Noguchi, Motoko; Niwa, Kenta; Kawase, Yoshiaki; Kono, Toru; Matsuda, Yoichi; Fujimoto, Hirokazu; Shibata, Hideo; Hayashizaki, Yoshihide; Sasaki, Hidetada

doi:10.1046/j.1365-2443.2000.00351.x

Cited by 196 publications

(148 citation statements)

References 40 publications

(47 reference statements)

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“…In ϩ/ϩ mice, differential methylation of the ICR in female and male germ cells is essentially fully established by the perinatal stage, with all copies of the ICR in female and male germ cells being hypoand hypermethylated, respectively (6,47). We obtained similar results for the mutant ICR, which was hypo-and hypermethylated in female and male germ cells of 17.5-dpc ϩ/Ϫ(P) fetuses, respectively.…”

Section: Resultssupporting

confidence: 72%

“…In addition we showed that the ICR is hypomethylated in perinatal female germ cells and methylated in male germ cells (Fig. 6) at the time of imprint establishment (6,47).…”

Section: Discussionmentioning

confidence: 73%

“…Differential methylation of the Igf2-H19 ICR, the establishment of which could be viewed as the imprinting mechanism itself, is laid down in the male and female germ lines (6,(45)(46)(47). It was shown that establishment of differential methylation is a function autonomous to the ICR (15), but the germ line-specific processes that establish this differential ICR methylation are undefined.…”

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confidence: 99%

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Role of CTCF Binding Sites in the Igf2/H19 Imprinting Control Region

Szabó

Tang

Silva

et al. 2004

Molecular and Cellular Biology

126

163

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A ϳ2.4-kb imprinting control region (ICR) regulates somatic monoallelic expression of the Igf2 and H19 genes. This is achieved through DNA methylation-dependent chromatin insulator and promoter silencing activities on the maternal and paternal chromosomes, respectively. In somatic cells, the hypomethylated maternally inherited ICR binds the insulator protein CTCF at four sites and blocks activity of the proximal Igf2 promoter by insulating it from its distal enhancers. CTCF binding is thought to play a direct role in inhibiting methylation of the ICR in female germ cells and in somatic cells and, therefore, in establishing and maintaining imprinting of the Igf2/H19 region. Here, we report on the effects of eliminating ICR CTCF binding by severely mutating all four sites in mice. We found that in the female and male germ lines, the mutant ICR remained hypomethylated and hypermethylated, respectively, showing that the CTCF binding sites are dispensable for imprinting establishment. Postfertilization, the maternal mutant ICR acquired methylation, which could be explained by loss of methylation inhibition, which is normally provided by CTCF binding. Adjacent regions in cis-the H19 promoter and gene-also acquired methylation, accompanied by downregulation of H19. This could be the result of a silencing effect of the methylated maternal ICR.

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Section: Resultssupporting

confidence: 72%

“…In addition we showed that the ICR is hypomethylated in perinatal female germ cells and methylated in male germ cells (Fig. 6) at the time of imprint establishment (6,47).…”

Section: Discussionmentioning

confidence: 73%

mentioning

confidence: 99%

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Role of CTCF Binding Sites in the Igf2/H19 Imprinting Control Region

Szabó

Tang

Silva

et al. 2004

Molecular and Cellular Biology

126

163

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“…Loss of methylation occurs shortly after the germ cells colonize the embryonic gonad (Davis et al, 2000;Hajkova et al, 2002). Establishment of new imprints by de-novo methylation of the DMR occurs in the prospermatogonia in the male germ line and during the oocyte growth phase in the ovary (Davis et al, 2000;Ueda et al, 2000;Lucifero et al, 2004;Li et al, 2004). Methylation of intracisternal A particles (IAP), LINE1 elements (L1) and minor satellite repeats also decreases in post-migratory germ cells but is not wholly removed (Hajkova et al, 2002;Lees-Murdock et al, 2003), which is important for maintaining transcriptional repression of transposons (Bourc'his and Bestor, 2004;Webster et al, 2005) and probably for the stability of the minor satellite DNA; remethylation of any demethylated elements also occurs in the prospermatogonia in males and the growing oocyte in females (Lees-Murdock et al, 2003;Lucifero et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Sex-specific promoters regulate Dnmt3L expression in mouse germ cells

et al. 2006

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BACKGROUND: Dnmt3L, a member of the DNA methyltransferase 3 family, lacks enzymatic activity but is required for de-novo methylation of imprinted genes in oocytes and for transposon repression in male germ cells. METHODS: We used northern blots, RT-PCR, 5¢ rapid amplification of complementary DNA (cDNA) ends (RACE), RNase H mapping, real-time/quantitative RT-PCR and in situ hybridization to identify and characterize Dnmt3L transcripts produced during germ cell development. RESULTS: Mouse Dnmt3L uses three sex-specific promoters, not the single promoter previously thought. A promoter active in prospermatogonia drives transcription of an mRNA encoding the full-length protein in perinatal testis, where de-novo methylation occurs. Late pachytene spermatocytes activate a second promoter in intron 9 of the Dnmt3L gene. After this stage, the predominant transcripts are three truncated mRNAs, which appear to be non-coding. We could also detect similar adult testis transcripts in humans. In the mouse ovary, an oocyte-specific promoter located in an intron of the neighbouring autoimmune regulator (Aire) gene produces a transcript with the full open reading frame (ORF). This is the only Dnmt3L transcript found in growing oocytes and is absent in the oocytes of Dnmt3L-/-females. CONCLUSIONS: Sex-specific promoters control Dnmt3L expression in the mouse germ line, mirroring the situation at the Dnmt1 and Dnmt3A loci.

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“…In the male germline, de novo DNA methylation of the four paternally methylated germline DMRs occurs progressively in mitotically arrested (G1/G0) prospermatogonia (or gonocytes) after embryonic day 14.5 (E14.5). Then, the paternal methylation imprints become fully established in prospermatogonia by the neonatal stage [17][18][19][20][21]. In the female germline, de novo DNA methylation initiates asynchronously at different germline DMRs during the oocyte growth phase [22,23].…”

Section: Life Cycle Of the Genomic Imprintsmentioning

confidence: 99%

Genomic imprinting in mammals: its life cycle, molecular mechanisms and reprogramming

Sasaki

2011

Cell Res

Self Cite

125

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Genomic imprinting, an epigenetic gene-marking phenomenon that occurs in the germline, leads to parental-origin-specific expression of a small subset of genes in mammals. Imprinting has a great impact on normal mammalian development, fetal growth, metabolism and adult behavior. The epigenetic imprints regarding the parental origin are established during male and female gametogenesis, passed to the zygote through fertilization, maintained throughout development and adult life, and erased in primordial germ cells before the new imprints are set. In this review, we focus on the recent discoveries on the mechanisms involved in the reprogramming and maintenance of the imprints. We also discuss the epigenetic changes that occur at imprinted loci in induced pluripotent stem cells.

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The paternal methylation imprint of the mouse H19 locus is acquired in the gonocyte stage during foetal testis development

Cited by 196 publications

References 40 publications

Role of CTCF Binding Sites in the Igf2/H19 Imprinting Control Region

Role of CTCF Binding Sites in the Igf2/H19 Imprinting Control Region

Sex-specific promoters regulate Dnmt3L expression in mouse germ cells

Genomic imprinting in mammals: its life cycle, molecular mechanisms and reprogramming

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