The chromosome 15 imprinting centre (IC) region has undergone multiple duplication events and contains an upstream exon of SNRPN that is deleted in all Angelman syndrome patients with an IC microdeletion

Färber, Claudia; Dittrich, Bärbel; Buiting, Karin; Horsthemke, Bernhard

doi:10.1093/hmg/8.2.337

Cited by 59 publications

(47 citation statements)

References 16 publications

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“…These investigators noted that the SNRPN transcription unit contains several upstream (U) exons located over 130 kb that splice into SNRPN exon 2, thereby replacing exon 1. Two of these U exons are located within the 880-bp AS-SRO (15)(16)(17). Extrapolating from these paternally derived transcripts detected in brain tissue, they speculated the existence of similar transcripts in oocytes that would transit the PWS-SRO and thereby contribute to the imprint-setting process.…”

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confidence: 99%

Angelman syndrome imprinting center encodes a transcriptional promoter

Lewis

Brant

Kramer

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Clusters of imprinted genes are often controlled by an imprinting center that is necessary for allele-specific gene expression and to reprogram parent-of-origin information between generations. An imprinted domain at 15q11–q13 is responsible for both Angelman syndrome (AS) and Prader–Willi syndrome (PWS), two clinically distinct neurodevelopmental disorders. Angelman syndrome arises from the lack of maternal contribution from the locus, whereas Prader–Willi syndrome results from the absence of paternally expressed genes. In some rare cases of PWS and AS, small deletions may lead to incorrect parent-of-origin allele identity. DNA sequences common to these deletions define a bipartite imprinting center for the AS–PWS locus. The PWS–smallest region of deletion overlap (SRO) element of the imprinting center activates expression of genes from the paternal allele. The AS–SRO element generates maternal allele identity by epigenetically inactivating the PWS–SRO in oocytes so that paternal genes are silenced on the future maternal allele. Here we have investigated functional activities of the AS–SRO, the element necessary for maternal allele identity. We find that, in humans, the AS–SRO is an oocyte-specific promoter that generates transcripts that transit the PWS–SRO. Similar upstream promoters were detected in bovine oocytes. This result is consistent with a model in which imprinting centers become DNA methylated and acquire maternal allele identity in oocytes in response to transiting transcription.

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mentioning

confidence: 99%

Angelman syndrome imprinting center encodes a transcriptional promoter

Lewis

Brant

Kramer

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…69,70 The SNRPN gene has a number of alternative transcripts, and AS-imprinting center overlaps with exons of such transcripts. 71,72 Therefore, one possible explanation for some cases would be that the deletions affect oocyte-specific alternative transcripts traversing the SNRPN ICR, and this results in a failure in imprint establishment. Prader-Willi syndrome (PWS) is another neurogenetic disorder that results from the abnormalities of the same imprinted cluster as AS.…”

Section: Childhood Diseases Associated With Imprint Establishment or mentioning

confidence: 99%

Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cell

Tomizawa

Sasaki

2012

J Hum Genet

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Genomic imprinting is an epigenetic gene-marking phenomenon that occurs in the germline, whereby genes are expressed from only one of the two parental copies in embryos and adults. Imprinting is essential for normal mammalian development and its disruption can cause various developmental defects and diseases. The process of imprinting in the germline involves DNA methylation of the imprint control regions (ICRs), and resulting parental-specific methylation imprints are maintained in the zygote and act as the marks controlling imprinted gene expression. Recent studies in mice have revealed new factors involved in imprint establishment during gametogenesis and maintenance during early development. Clinical studies have identified cases of imprinting disorders where involvement of factors shared by multiple ICRs for establishment or maintenance is suspected. These include Beckwith-Wiedemann syndrome, transient neonatal diabetes, Silver-Russell syndrome and others. More severe disruptions can lead to recurrent molar pregnancy, miscarriage or infertility. Imprinting defects may also occur during assisted reproductive technology or cell reprogramming. In this review, we summarize our current knowledge on the mechanisms of imprint establishment and maintenance, and discuss the relationship with various human disorders.

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“…2,3 In 2000 we identified C15orf2, which is a 7.5 kb intronless gene located B300 kb upstream of the major SNURF -SNRPN start site. 4 C15orf2 has a 3.5 kb open reading frame encoding an 1156 amino-acid protein of unknown function.…”

Section: Introductionmentioning

confidence: 99%

Expression of SNURF–SNRPN upstream transcripts and epigenetic regulatory genes during human spermatogenesis

et al. 2009

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The imprinted domain in human 15q11-q13 is controlled by a bipartite imprinting centre (IC), which overlaps the 5 0 part of the paternally expressed SNURF -SNRPN gene. We have recently described two novel genes upstream of SNURF-SNRPN (PWRN1 and PWRN2), which are biallelically expressed in the testis. We have now found that PWRN1 represents an alternative 5 0 part of SNURF -SNRPN, and that its expression in the brain is imprinted. To determine when the locus is activated during spermatogenesis and which factors are involved in this process, we have mined gene-expression data of testicular biopsies from men with different types of spermatogenic failure. Whereas PWRN1-SNURF-SNRPN and PWRN2 are expressed in post-meiotic germ cells only, a hitherto undetected SNURF-SNRPN upstream transcript is expressed already at meiosis. Several epigenetic factors (eg, MBD1 and MBD2 isoforms, MBD3L1, SUVH39H2, BRDT, and EZH2) are upregulated at specific stages of spermatogenesis, suggesting that they play an important role in the epigenetic reprogramming during spermatogenesis.

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The chromosome 15 imprinting centre (IC) region has undergone multiple duplication events and contains an upstream exon of SNRPN that is deleted in all Angelman syndrome patients with an IC microdeletion

Cited by 59 publications

References 16 publications

Angelman syndrome imprinting center encodes a transcriptional promoter

Angelman syndrome imprinting center encodes a transcriptional promoter

Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cell

Expression of SNURF–SNRPN upstream transcripts and epigenetic regulatory genes during human spermatogenesis

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