The Prader-Willi/Angelman imprinted domain and its control center

Kantor, Boris; Shemer, Ruth; Razin, Aharon

doi:10.1159/000090845

Cited by 42 publications

(27 citation statements)

References 73 publications

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“…This region is controlled by elements within the SNURF-SNRPN promoter, which is composed of a bidirectional activator responsible for a number of genes in this locus [65], making it the epicenter of regulation in this imprinted cluster. It is a bipartite imprinting control center; that is, two (reciprocal) ICRs are at play here—the 4.3 kb PWS-IC (which includes Exon 1 and the promoter of the SNURF-SNRPN gene), and the 0.88 kb AS-IC (located 35 kb upstream) [70].…”

Section: Snurf-snrpnmentioning

confidence: 99%

Long Noncoding RNAs in Imprinting and X Chromosome Inactivation

2014

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The field of long noncoding RNA (lncRNA) research has been rapidly advancing in recent years. Technological advancements and deep-sequencing of the transcriptome have facilitated the identification of numerous new lncRNAs, many with unusual properties, however, the function of most of these molecules is still largely unknown. Some evidence suggests that several of these lncRNAs may regulate their own transcription in cis, and that of nearby genes, by recruiting remodeling factors to local chromatin. Notably, lncRNAs are known to exist at many imprinted gene clusters. Genomic imprinting is a complex and highly regulated process resulting in the monoallelic silencing of certain genes, based on the parent-of-origin of the allele. It is thought that lncRNAs may regulate many imprinted loci, however, the mechanism by which they exert such influence is poorly understood. This review will discuss what is known about the lncRNAs of major imprinted loci, and the roles they play in the regulation of imprinting.

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Section: Snurf-snrpnmentioning

confidence: 99%

Long Noncoding RNAs in Imprinting and X Chromosome Inactivation

2014

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“…Clinically, determination of the parent of origin of chromosomal errors such as uniparental disomy can be significant for chromosomes with important imprinted loci, e.g. in Prader-Willi/Angelman syndromes (Curran et al 2005;Kantor et al 2006;Sartori et al 2008). Determining the phase of origin also has clinical ramification when considering obstetric outcomes of mosaic pregnancies: Those of meiotic origin often lead to specific phenotypes such as intra-uterine growth retardation, excessive birth weight and late pregnancy loss whereas those of mitotic origin proceed largely uneventfully to term (Herbert et al 1995;Wolstenholme and Angell 2000;Clouston et al 2002).…”

Section: Introductionmentioning

confidence: 99%

An algorithm for determining the origin of trisomy and the positions of chiasmata from SNP genotype data

et al. 2011

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Trisomy causes mental retardation, pregnancy loss, IVF failure, uniparental disomy and several other pathologies, and its accurate detection is thus clinically essential. Most trisomies arise at meiosis I and are associated with increasing maternal age and reduction or alteration in recombination patterns. Investigations into the relationship between trisomy and meiotic recombination have used short tandem repeat markers; however, this approach is limited by the resolution with which the position of crossovers can identified. As cytogenetics enters the post-genomic era, recent work has used array comparative genomic hybridisation (aCGH) to screen for trisomy of all 24 chromosomes, determining chromosome copy number by dosage analysis. However, aCGH has a fundamental drawback for studying the aetiology of trisomy since neither the parent and phase of origin nor uniparental disomy can be ascertained. The development of SNP microarrays has made it possible to analyse multiple loci for sequence variation, and the proprietary software provided can determine the presence of aneuploidy by algorithms based on fluorescence intensity. To the best of our knowledge, however, such software is not equipped to determine the phase of origin of the error or the position of any chiasmata. In this study, therefore, we present an algorithm to determine the parent of origin, the phase of origin and the location of chiasmata in a series of nine "trisomy triplets" (i.e. samples derived from father, mother and their trisomic foetus). Novel adaptations of well-established principles are applied along with a simple algorithm written in Microsoft Excel for visualisation of the results. Such analysis has a range of applications in preimplantation and prenatal diagnosis.

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“…Imprinting of the PWS/AS domain is regulated through a bipartite cis-acting imprinting center (IC), comprised of the PWS-IC and the AS-IC within and upstream of the SNRPN promoter (Buiting et al 1995Ohta et al 1999). The IC is marked epigenetically according to the parent of origin, which results in differential allelic expression of genes across the PWS/AS domain (Kantor et al 2006). …”

mentioning

confidence: 99%

Deficiency of Rbbp1/Arid4a and Rbbp1l1/Arid4b alters epigenetic modifications and suppresses an imprinting defect in the PWS/AS domain

Wu¹,

Tsai²,

Beaudet³

2006

Genes Dev.

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Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by deficiency of imprinted gene expression from paternal or maternal chromosome 15q11-q13, respectively. Genomic imprinting of the PWS/AS domain is regulated through a bipartite cis-acting imprinting center (PWS-IC/AS-IC) within and upstream of the SNRPN promoter. Here, we show that two Rb-binding protein-related genes, Rbbp1/Arid4a and Rbbp1l1/Arid4b, are involved in the regulation of imprinting of the IC. We recovered these two genes from gene trap mutagenesis selecting for altered expression of an Snrpn-EGFP fusion gene strategy. RBBP1/ARID4A is an Rb-binding protein. RBBP1/ARID4A interacts with RBBP1L1/ARID4B and with the Snrpn promoter, implying that both are part of a protein complex. To further elucidate their roles on regulation of imprinting, we deleted the Rbbp1/Arid4a and Rbbp1l1/Arid4b genes in mice. Combined homozygous deficiency for Rbbp1/Arid4a and heterozygous deficiency for Rbbp1l1/Arid4b altered epigenetic modifications at the PWS-IC with reduced trimethylation of histone H4K20 and H3K9 and reduced DNA methylation, changing the maternal allele toward a more paternal epigenotype. Importantly, mutations of Rbbp1/Arid4a, Rbbp1l1/Arid4b, or Rb suppressed an AS imprinting defect caused by a mutation at the AS-IC. These data identify Rbbp1/Arid4a and Rbbp1l1/Arid4b as new members of epigenetic complexes regulating genomic imprinting at the PWS/AS domain.

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The Prader-Willi/Angelman imprinted domain and its control center

Cited by 42 publications

References 73 publications

Long Noncoding RNAs in Imprinting and X Chromosome Inactivation

Long Noncoding RNAs in Imprinting and X Chromosome Inactivation

An algorithm for determining the origin of trisomy and the positions of chiasmata from SNP genotype data

Deficiency of Rbbp1/Arid4a and Rbbp1l1/Arid4b alters epigenetic modifications and suppresses an imprinting defect in the PWS/AS domain

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