An ICE pattern crystallizes

Spahn, Laura; Barlow, Denise P.

doi:10.1038/ng0903-11

Cited by 76 publications

(55 citation statements)

References 16 publications

(30 reference statements)

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“…At both sites, differential methylation of the maternal allele is established in oocytes and maintained after fertilisation and into adulthood in all somatic tissues (Liu et al 2000b, Coombes et al 2003. Such germline differences in DNA methylation are characteristic of imprinting control regions (ICRs; Spahn & Barlow 2003). A third DMR located at the Nesp promoter is unmethylated in oocytes and sperm, but acquires methylation on the paternal allele during embryonic development (Liu et al 2000b, Coombes et al 2003.…”

Section: Non-coding Transcripts and Imprinting Marksmentioning

confidence: 99%

Physiological functions of the imprinted Gnas locus and its protein variants Gαs and XLαs in human and mouse

Plagge

Kelsey

Germain‐Lee

2007

Journal of Endocrinology

104

137

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The stimulatory a-subunit of trimeric G-proteins Ga s , which upon ligand binding to seven-transmembrane receptors activates adenylyl cyclases to produce the second messenger cAMP, constitutes one of the archetypal signal transduction molecules that have been studied in much detail. Over the past few years, however, genetic as well as biochemical approaches have led to a range of novel insights into the Ga s encoding guanine nucleotide binding protein, a-stimulating (Gnas) locus, its alternative protein products and its regulation by genomic imprinting, which leads to monoallelic, parental origin-dependent expression of the various transcripts. Here, we summarise the major characteristics of this complex gene locus and describe the physiological roles of Ga s and its 'extra large' variant XLa s at post-natal and adult stages as defined by genetic mutations. Opposite and potentially antagonistic functions of the two proteins in the regulation of energy homeostasis and metabolism have been identified in Gnasand Gnasxl (XLa s )-deficient mice, which are characterised by obesity and leanness respectively. A comparison of findings in mice with symptoms of the corresponding human genetic disease 'Albright's hereditary osteodystrophy'/'pseudohypoparathyroidism' indicates highly conserved functions as well as unresolved phenotypic differences.

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Section: Non-coding Transcripts and Imprinting Marksmentioning

confidence: 99%

Physiological functions of the imprinted Gnas locus and its protein variants Gαs and XLαs in human and mouse

Plagge

Kelsey

Germain‐Lee

2007

Journal of Endocrinology

104

137

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“…Imprinted genes are expressed exclusively or preferentially from only one of the two parental alleles, tend to occur in clusters (imprinted domains), and are frequently involved in growth regulation and development, with paternally expressed genes often coding for growth promoters and maternally expressed genes often coding for growth suppressors (Barlow and Bartolomei, 2014;Bartolomei and Ferguson-Smith, 2011;Li and Sasaki, 2011;Tycko and Morison, 2002). Monoallelic expression of genes present in an imprinted domain is controlled by cis-acting short DNA sequences known as imprinting control regions (ICRs) or imprinting centers (ICs) that can function over long genomic distances (Spahn and Barlow, 2003;Verona et al, 2003). As first demonstrated for the H19/Igf2 (Thorvaldsen et al, 1998), the Igf2r/Air (Sleutels et al, 2002) and KvDMR1 imprinted domains (Fitzpatrick et al, 2002), targeted deletion of these sequences in the mouse results in disruption of imprinting.…”

Section: Introductionmentioning

confidence: 99%

Blocked transcription through KvDMR1 results in absence of methylation and gene silencing resembling Beckwith-Wiedemann syndrome

et al. 2017

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The maternally methylated KvDMR1 ICR regulates imprinted expression of a cluster of maternally expressed genes on human chromosome 11p15.5. Disruption of imprinting leads to BeckwithWiedemann syndrome (BWS), an overgrowth and cancer predisposition condition. In the majority of individuals with BWS, maternal-specific methylation at KvDMR1 is absent and genes under its control are repressed. We analyzed a mouse model carrying a poly(A) truncation cassette inserted to prevent RNA transcripts from elongation through KvDMR1. Maternal inheritance of this mutation resulted in absence of DNA methylation at KvDMR1, which led to biallelic expression of Kcnq1ot1 and suppression of maternally expressed genes. This study provides further evidence that transcription is required for establishment of methylation at maternal gametic DMRs. More importantly, this mouse model recapitulates the molecular phenotypic characteristics of the most common form of BWS, including loss of methylation at KvDMR1 and biallelic repression of Cdkn1c, suggesting that deficiency of maternal transcription through KvDMR1 may be an underlying cause of some BWS cases.

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“…The imprinted genes are clustered in specific regions of chromosomes, and each imprinted domain is usually controlled by small genomic regions, termed imprinting control regions (ICRs) (Brannan and Bartolomei 1999;Spahn and Barlow 2003). These ICRs are usually located in CpG-rich regions near the promoters of imprinted genes and methylated differentially between two parental alleles.…”

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confidence: 99%

Identification of clustered YY1 binding sites in imprinting control regions

Kim¹,

Hinz²,

Bergmann³

et al. 2006

Genome Res.

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Mammalian genomic imprinting is regulated by imprinting control regions (ICRs) that are usually associated with tandem arrays of transcription factor binding sites. In this study, the sequence features derived from a tandem array of YY1 binding sites of Peg3-DMR (differentially methylated region) led us to identify three additional clustered YY1 binding sites, which are also localized within the DMRs of Xist, Tsix, and Nespas. These regions have been shown to play a critical role as ICRs for the regulation of surrounding genes. These ICRs have maintained a tandem array of YY1 binding sites during mammalian evolution. The in vivo binding of YY1 to these regions is allele specific and only to the unmethylated active alleles. Promoter/enhancer assays suggest that a tandem array of YY1 binding sites function as a potential orientation-dependent enhancer. Insulator assays revealed that the enhancer-blocking activity is detected only in the YY1 binding sites of Peg3-DMR but not in the YY1 binding sites of other DMRs. Overall, our identification of three additional clustered YY1 binding sites in imprinted domains suggests a significant role for YY1 in mammalian genomic imprinting.

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An ICE pattern crystallizes

Abstract: Identification of a new imprinting control element (ICE) on mouse chromosome 12 brings the total to five. Common features of imprinting mechanisms suggest a general model of ICE function.

Cited by 76 publications

References 16 publications

Physiological functions of the imprinted Gnas locus and its protein variants Gαs and XLαs in human and mouse

Physiological functions of the imprinted Gnas locus and its protein variants Gαs and XLαs in human and mouse

Blocked transcription through KvDMR1 results in absence of methylation and gene silencing resembling Beckwith-Wiedemann syndrome

Identification of clustered YY1 binding sites in imprinting control regions

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