Sequence and functional comparison in the Beckwith-Wiedemann region: implications for a novel imprinting centre and extended imprinting

Engemann, Sabine; Strödicke, Martin; Paulsen, Martina; Franck, Olivia; Reinhardt, Richard; Lane, Natasha; Reik, Wolf; Walter, Jörn

doi:10.1093/hmg/9.18.2691

Cited by 135 publications

(116 citation statements)

References 65 publications

Supporting

Mentioning

108

Contrasting

Unclassified

Order By: Relevance

“…9 However, in 60% of cases, BWS is caused by hypomethylation of a second differentially methylated region at 11p15 (ICR2), which regulates expression of the transcript KCNQ1OT1. 10,11 This region has not been found to be epigenetically altered in patients with SRS.…”

Section: Introductionmentioning

confidence: 96%

IGF2/H19 hypomethylation in Silver–Russell syndrome and isolated hemihypoplasia

et al. 2008

View full text Add to dashboard Cite

Silver-Russell syndrome (SRS) is a clinically and genetically heterogeneous syndrome characterized by severe pre and postnatal growth retardation, body asymmetry and a typical facial phenotype with a triangular face and relative macrocephaly. In 30% of patients, the differentially methylated IGF2/H19 imprinting center region (ICR1) on chromosome 11p15 was found to be hypomethylated, as determined by Southern blot analysis of an HpaII restriction site close to the third CTCF-binding site (CTS3) within ICR1. Using bisulfite treatment and a real-time PCR-based methylation assay (QAMA), we analyzed the third and sixth CTCF-binding sites (CTS3, CTS6) in 5 patients with CTS3 hypomethylation, in 14 patients who were suspected to have SRS but were normal by Southern blot analysis, and in 1 patient with body asymmetry without any other features of SRS or Beckwith-Wiedemann syndrome (BWS). In all 5 patients with CTS3 hypomethylation, in 5 of 14 patients who were judged to be normal at CTS3 by Southern blot analysis and in the patient with isolated body asymmetry, we found CTS3 and CTS6 hypomethylation by QAMA. Using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), we obtained similar results at four additional ICR1 sites in the CTS6 region. These results show that ICR1 hypomethylation occurs more often in SRS patients than as previously thought as well as in isolated hemihypoplasia. Furthermore, we show that methylation analysis by QAMA and MLPA is more sensitive in detecting ICR1 hypomethylation than Southern blot analysis of CTS3.

show abstract

Section: Introductionmentioning

confidence: 96%

IGF2/H19 hypomethylation in Silver–Russell syndrome and isolated hemihypoplasia

et al. 2008

View full text Add to dashboard Cite

show abstract

“…2B) are maternally duplicated for the hypomethylated Igf2/H19 ICR 21,27,42,43 and hypermethylated KvDMR1 ICR. 19,33,34 PatDup.dist7 embryos are paternally duplicated for the hypermethylated H19/Igf2 ICR and hypomethylated KvDMR1 (Fig. 2C).…”

Section: Resultsmentioning

confidence: 99%

“…CTCF binding is inhibited in the paternal ICR allele by DNA methylation, allowing Igf2 promoter access to the enhancers. [28][29][30][31][32] The maternally methylated Kv differentially methylated region (KvDMR1) 19,33,34 controls the Cdkn1c/Kcnq1 imprinted domain. KvDMR1 is a CpG island in the intron of the Kcnq1 transcript.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

MIRA-SNuPE, a quantitative, multiplex method for measuring allele-specific DNA methylation

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Six genes: Ascl2, Tspan32, Cd81, Tssc4, Nap1l4 and Osbpl5 only show imprinted expression in placental tissues. 42,44 Recent studies however, challenge the imprinted status of Tssc4, Nap1l4 and Osbpl5, since their high expression in the maternal decidua invalidates their analysis in mouse placenta. 39,45,46 The Nespas macro lncRNA silences the Gnas imprinted gene cluster.…”

Section: How Can Non-coding Rnas Function In Gene Regulation?mentioning

confidence: 99%