ArticleFrontiers in genetics2016
Epigenetic Characterization of CDKN1C in Placenta Samples from Non-syndromic Intrauterine Growth Restriction.
Article in Frontiers in genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 27 citations in OpenAlex.
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- Sex-differentiated placental methylation and gene expression regulation has implications for neonatal traits and adult diseases.Nature communications · 2025Article
- Identification and characterization of an enhancer element regulating expression of Cdkn1c (p57 gene).Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNA.Epigenetics · 2024Article
- Epigenetic control of the imprinted growth regulatorEpigenetics · 2023Article
- iSMOD: an integrative browser for image-based single-cell multi-omics data.Nucleic acids research · 2023Article
- Single-nuclei RNA sequencing (snRNA-seq) uncovers trophoblast cell types and lineages in the mature bovine placenta.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The role of CTCF in the organization of the centromeric 11p15 imprinted domain interactome.Nucleic acids research · 2021Article
- Deregulation of imprinted genes expression and epigenetic regulators in placental tissue from intrauterine growth restriction.Journal of assisted reproduction and genetics · 2021Article
- New Horizons in Short Children Born Small for Gestational Age.Frontiers in pediatrics · 2021Review
- The role of ZFP57 and additional KRAB-zinc finger proteins in the maintenance of human imprinted methylation and multi-locus imprinting disturbances.Nucleic acids research · 2020Article
- Differences in expression rather than methylation at placenta-specific imprinted loci is associated with intrauterine growth restriction.Clinical epigenetics · 2019Article
- Analysis ofF1000Research · 2019Review
- Profiling of oxBS-450K 5-hydroxymethylcytosine in human placenta and brain reveals enrichment at imprinted loci.Epigenetics · 2018Article
- H3K27 acetylation and gene expression analysis reveals differences in placental chromatin activity in fetal growth restriction.Clinical epigenetics · 2018Article
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cyclin-dependent kinase (CDK)-inhibitor 1C (CDKN1C) gene is expressed from the maternal allele and is located within the centromeric imprinted domain at chromosome 11p15. It is a negative regulator of proliferation, with loss-of-function mutations associated with the overgrowth disorder Beckwith-Wiedemann syndrome. Recently, gain-of-function mutations within the PCNA domain have been described in two disorders characterized by growth failure, namely IMAGe (intra-uterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital abnormalities) syndrome and Silver-Russell syndrome (SRS). Over-expression of CDKN1C by maternally inherited microduplications also results in SRS, suggesting that in addition to activating mutations this gene may regulate growth by changes in dosage. To determine if CDKN1C is involved in non-syndromic IUGR we compared the expression and DNA methylation levels in a large cohort of placental biopsies from IUGR and uneventful pregnancies. We observe higher levels of expression of CDKN1C in IUGR placentas compared to those of controls. All placenta biopsies heterozygous for the PAPA repeat sequence in exon 2 showed appropriate monoallelic expression and no mutations in the PCNA domain were observed. The expression profile was independent of both genetic or methylation variation in the minimal CDKN1C promoter interval and of methylation of the cis-acting maternally methylated region associated with the neighboring KCNQ1OT1 non-coding RNA. Chromatin immunoprecipitation revealed binding sites for CTCF within the unmethylated CDKN1C gene body CpG island and putative enhancer regions, associated with the canonical enhancer histone signature, H3K4me1 and H3K27ac, located ∼58 and 360 kb away. Using 3C-PCR we identify constitutive higher-order chromatin loops that occur between one of these putative enhancer regions and CDKN1C in human placenta tissues, which we propose facilitates expression.
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