Methylation at mouse Cdkn1c is acquired during postimplantation development and functions to maintain imprinted expression

Bhogal, Balpreet; Arnaudo, Anna M.; Dymkowski, Alyson; Best, Alison; Davis, Tamara L.

doi:10.1016/j.ygeno.2004.08.004

Cited by 63 publications

(90 citation statements)

References 40 publications

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“…Indeed even for Cdkn1c, its paternal-specific methylation is not inherited from the gametes but is established post-implantation during the wave of de novo genome methylation (Engemann et al 2000). Analysis of preimplantation embryos revealed maternal-specific expression of Cdkn1c prior to the establishment of its differential methylation, implying that methylation does not contribute to the establishment of the imprinted state at Cdkn1c, but adds another level of stability, effectively reinforcing the imprinted state within the embryo (Bhogal et al 2004).…”

Section: Genes and Development 1277mentioning

confidence: 99%

Elongation of theKcnq1ot1transcript is required for genomic imprinting of neighboring genes

Mancini‐DiNardo

Steele²,

Levorse³

et al. 2006

Genes Dev.

406

380

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The imprinted gene cluster at the telomeric end of mouse chromosome 7 contains a differentially methylated CpG island, KvDMR, that is required for the imprinting of multiple genes, including the genes encoding the maternally expressed placental-specific transcription factor ASCL2, the cyclin-dependent kinase CDKN1C, and the potassium channel KCNQ1. The KvDMR, which maps within intron 10 of Kcnq1, contains the promoter for a paternally expressed, noncoding, antisense transcript, Kcnq1ot1. A 244-base-pair deletion of the promoter on the paternal allele leads to the derepression of all silent genes tested. To distinguish between the loss of silencing as the consequence of the absence of transcription or the transcript itself, we prematurely truncated the Kcnq1ot1 transcript by inserting a transcriptional stop signal downstream of the promoter. We show that the lack of a full-length Kcnq1ot1 transcript on the paternal chromosome leads to the expression of genes that are normally paternally repressed. Finally, we demonstrate that five highly conserved repeats residing at the 5 end of the Kcnq1ot1 transcript are not required for imprinting at this locus.

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Section: Genes and Development 1277mentioning

confidence: 99%

Elongation of theKcnq1ot1transcript is required for genomic imprinting of neighboring genes

Mancini‐DiNardo

Steele²,

Levorse³

et al. 2006

Genes Dev.

406

380

View full text Add to dashboard Cite

show abstract

“…One example of a DMR is in the promoter of the maternally expressed Cdkn1c gene. This promoter becomes methylated on the paternal allele in the post-implantation embryo, after imprinting is established at this locus (Bhogal et al 2004). Further, the promoter of the maternally expressed Igf2r gene is methylated on the paternal allele, and this DNA methylation also occurs after establishment of imprinting (Stö ger et al 1993).…”

Section: Differential Marking Of Parental Allelesmentioning

confidence: 99%

Genomic imprinting: employing and avoiding epigenetic processes

Bartolomei¹

2009

Genes Dev.

227

202

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Genomic imprinting refers to an epigenetic mark that distinguishes parental alleles and results in a monoallelic, parental-specific expression pattern in mammals. Few phenomena in nature depend more on epigenetic mechanisms while at the same time evading them. The alleles of imprinted genes are marked epigenetically at discrete elements termed imprinting control regions (ICRs) with their parental origin in gametes through the use of DNA methylation, at the very least. Imprinted gene expression is subsequently maintained using noncoding RNAs, histone modifications, insulators, and higher-order chromatin structure. Avoidance is manifest when imprinted genes evade the genome-wide reprogramming that occurs after fertilization and remain marked with their parental origin. This review summarizes what is known about the establishment and maintenance of imprinting marks and discusses the mechanisms of imprinting in clusters. Additionally, the evolution of imprinted gene clusters is described. While considerable information regarding epigenetic control of imprinting has been obtained recently, much remains to be learned.

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“…It contains two differentially methylated regions (DMRs): one is a germline imprint which acts as the imprinting centre (IC2) and contains the promoter of the non-coding Kcnq1ot1 gene; the other is a secondary imprint upstream of the cell cycle regulator Cdkn1c which is not established until postimplantation stages of development (Bhogal et al, 2004;Engemann et al, 2000;Fitzpatrick et al, 2002). The other genes in the cluster have no associated differential DNA methylation (Lewis et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic dynamics of theKcnq1imprinted domain in the early embryo

et al. 2006

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The mouse Kcnq1 imprinted domain is located on distal chromosome 7 and contains several imprinted genes that are paternally repressed. Repression of these genes is regulated by a non-coding antisense transcript, Kcnq1ot1, which is paternally expressed. Maternal repression of Kcnq1ot1 is controlled by DNA methylation originating in the oocyte. Some genes in the region are imprinted only in the placenta, whereas others are imprinted in both extra-embryonic and embryonic lineages. Here, we show that Kcnq1ot1 is paternally expressed in preimplantation embryos from the two-cell stage, and that ubiquitously imprinted genes proximal to Kcnq1ot1 are already repressed in blastocysts, ES cells and TS cells. Repressive histone marks such as H3K27me3 are present on the paternal allele of these genes in both ES and TS cells. Placentally imprinted genes that are distal to Kcnq1ot1, by contrast, are not imprinted in blastocysts, ES or TS cells. In these genes, paternal silencing and differential histone marks arise during differentiation of the trophoblast lineage between E4.5 and E7.5. Our findings show that the dynamics during preimplantation development of gene inactivation and acquisition of repressive histone marks in ubiquitously imprinted genes of the Kcnq1 domain are very similar to those of imprinted X inactivation. By contrast, genes that are only imprinted in the placenta, while regulated by the same non-coding RNA transcript Kcnq1ot1, undergo epigenetic inactivation during differentiation of the trophoblast lineage. Our findings establish a model for how epigenetic gene silencing by non-coding RNA may depend on distance from the non-coding RNA and on lineage and differentiation specific factors.

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Methylation at mouse Cdkn1c is acquired during postimplantation development and functions to maintain imprinted expression

Cited by 63 publications

References 40 publications

Elongation of theKcnq1ot1transcript is required for genomic imprinting of neighboring genes

Elongation of theKcnq1ot1transcript is required for genomic imprinting of neighboring genes

Genomic imprinting: employing and avoiding epigenetic processes

Epigenetic dynamics of theKcnq1imprinted domain in the early embryo

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