Genomic Imprinting—The Struggle of the Genders at the Molecular Level

Jurkowska, Renata Z.; Jeltsch, Albert

doi:10.1002/anie.201307005

Cited by 8 publications

(4 citation statements)

References 126 publications

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“…Genomic imprinting is a unique epigenetic process that involves differential DNA methylation on parental alleles at so‐called imprinting centers (ICs). The differential methylation leads to a monoallelic expression of genes (either maternal or paternal) under the control of this IC without altering the DNA sequence . Usually, each IC controls several protein coding and ncRNA genes, some of which are expressed from the paternal and some from the maternal allele.…”

Section: Imprinting and Imprinting Diseasesmentioning

confidence: 99%

Correction of aberrant imprinting by allele‐specific epigenome editing

Bashtrykov

Kungulovski

Jeltsch

2015

Clin Pharma and Therapeutics

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Imprinting disorders are caused by the loss of the normal allele-specific DNA methylation at imprinting centers. Epigenetic editing is a promising approach to alter DNA methylation at defined genomic target regions. The novel development of CRISPR-Cas9-based DNA binding domains may allow for an allele-specific editing of DNA methylation at imprinted loci, for the first time offering a rational approach for correction of the molecular defects in imprinting disorders.

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Section: Imprinting and Imprinting Diseasesmentioning

confidence: 99%

Correction of aberrant imprinting by allele‐specific epigenome editing

Bashtrykov

Kungulovski

Jeltsch

2015

Clin Pharma and Therapeutics

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“…According to the parental conflict theory, imprinting has evolved to serve the conflicting interests of the father and the mother; paternally expressed genes promote fetal growth to ensure the viability of the present offspring, whereas maternally expressed genes restrict fetal growth to preserve the mother’s resources to her future offspring ( 10 ). Herein, we investigated the growth and endocrine features of patient with long QT syndrome (LQTS) due to loss-of-function mutations in KCNQ1 .…”

Section: Introductionmentioning

confidence: 99%

The Role of KCNQ1 Mutations and Maternal Beta Blocker Use During Pregnancy in the Growth of Children With Long QT Syndrome

et al. 2018

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ObjectiveTwo missense mutations in KCNQ1, an imprinted gene that encodes the alpha subunit of the voltage-gated potassium channel Kv7.1, cause autosomal dominant growth hormone deficiency and maternally inherited gingival fibromatosis. We evaluated endocrine features, birth size, and subsequent somatic growth of patients with long QT syndrome 1 (LQT1) due to loss-of-function mutations in KCNQ1.DesignMedical records of 104 patients with LQT1 in a single tertiary care center between 1995 and 2015 were retrospectively reviewed.MethodsClinical and endocrine data of the LQT1 patients were included in the analyses.ResultsAt birth, patients with a maternally inherited mutation (n = 52) were shorter than those with paternal inheritance of the mutation (n = 29) (birth length, −0.70 ± 1.1 SDS vs. −0.2 ± 1.0 SDS, P < 0.05). Further analyses showed, however, that only newborns (n = 19) of mothers who had received beta blockers during pregnancy were shorter and lighter at birth than those with paternal inheritance of the mutation (n = 29) (−0.89 ± 1.0 SDS vs. −0.20 ± 1.0 SDS, P < 0.05; and 3,173 ± 469 vs. 3,515 ± 466 g, P < 0.05). Maternal beta blocker treatment during the pregnancy was also associated with lower cord blood TSH levels (P = 0.011) and significant catch-up growth during the first year of life (Δ0.08 SDS/month, P = 0.004). Later, childhood growth of the patients was unremarkable.ConclusionLoss-of-function mutations in KCNQ1 are not associated with abnormalities in growth, whereas maternal beta blocker use during pregnancy seems to modify prenatal growth of LQT1 patients—a phenomenon followed by catch-up growth after birth.

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“…These epigenetic mechanisms extend the information content of the genome and mediate the heritable propagation of transcriptional cellular programs and cellular identity, which is a cornerstone of organismic development [ 1 - 5 ]. Examples of inherited epigenetic signals [ 6 ] include imprinting and X-chromosome inactivation in mammals [ 7 , 8 ], and trans-generational inheritance of epigenetic states recently shown in plants [ 9 ] or worms [ 10 ]. Epigenetic signaling is not only essential for normal development but it plays a central role in the onset of diseases including cancer as well [ 11 - 14 ].…”

Section: Introductionmentioning

confidence: 99%

Targeted epigenome editing of an endogenous locus with chromatin modifiers is not stably maintained

Kungulovski

Nunna

Thomas

et al. 2015

Epigenetics & Chromatin

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BackgroundDNA methylation and histone 3 lysine 9 (H3K9) methylation are considered as epigenetic marks that can be inherited through cell divisions. To explore the functional consequences and stability of these modifications, we employed targeted installment of DNA methylation and H3K9 methylation in the vascular endothelial growth factor A (VEGF-A) promoter using catalytic domains of DNA or H3K9 methyltransferases that are fused to a zinc finger protein which binds a site in the VEGF-A promoter.ResultsExpression of the targeted DNA and H3K9 methyltransferases caused dense deposition of DNA methylation or H3K9 di- and trimethylation in the promoter of VEGF-A and downregulation of VEGF-A gene expression. We did not observe positive feedback between DNA methylation and H3K9 methylation. Upon loss of the targeted methyltransferases from the cells, the epigenetic marks, chromatin environment, and gene expression levels returned to their original state, indicating that both methylation marks were not stably propagated after their installment.ConclusionsThe clear anti-correlation between DNA or H3K9 methylation and gene expression suggests a direct role of these marks in transcriptional control. The lack of maintenance of the transiently induced silenced chromatin state suggests that the stability of epigenetic signaling is based on an epigenetic network consisting of several molecular marks. Therefore, for stable reprogramming, either multivalent deposition of functionally related epigenetic marks or longer-lasting trigger stimuli might be necessary.Electronic supplementary materialThe online version of this article (doi:10.1186/s13072-015-0002-z) contains supplementary material, which is available to authorized users.

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Genomic Imprinting—The Struggle of the Genders at the Molecular Level

Cited by 8 publications

References 126 publications

Correction of aberrant imprinting by allele‐specific epigenome editing

Correction of aberrant imprinting by allele‐specific epigenome editing

The Role of KCNQ1 Mutations and Maternal Beta Blocker Use During Pregnancy in the Growth of Children With Long QT Syndrome

Targeted epigenome editing of an endogenous locus with chromatin modifiers is not stably maintained

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