Transcriptional profiling at the DLK1/MEG3 domain explains clinical overlap between imprinting disorders

Science Advances
Walid Abi HabibIrène Netchine

Abstract

Imprinting disorders (IDs) often affect growth in humans, leading to diseases with overlapping features, regardless of the genomic region affected. IDs related to hypomethylation of the human 14q32.2 region and its DLK1/MEG3 domain are associated with Temple syndrome (TS14). TS14 is a rare type of growth retardation, the clinical signs of which overlap considerably with those of Silver-Russell syndrome (SRS), another ID related to IGF2 down-regulation at 11p15.5 region. We show that 14q32.2 hypomethylation affects expression, not only for genes at this locus but also for other imprinted genes, and especially lowers IGF2 levels at 11p15.5. Furthermore, expression of nonimprinted genes is also affected, some of which are also deregulated in SRS patients. These findings highlight the epigenetic regulation of gene expression at the DLK1/MEG3 domain. Expression profiling of TS14 and SRS patients highlights common signatures, which may account for the clinical overlap observed between TS14 and SRS.

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Citations

Sep 27, 2019·Frontiers in Endocrinology·Jesús ArgenteRoland Pfäffle
Jul 18, 2020·The Journal of Clinical Endocrinology and Metabolism·Luciana MontenegroJesús Argente
Aug 29, 2019·Archives of Endocrinology and Metabolism·Ana Pinheiro Machado CantonAna Claudia Latronico
Dec 22, 2019·Epigenetics & Chromatin·Brenna A LaBarreLaura Elnitski
Jul 5, 2019·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Samuel HamiltonMichel Bernier
Mar 1, 2021·The Journal of Clinical Endocrinology and Metabolism·Clive J PetryDavid B Dunger
Jul 20, 2021·European Journal of Human Genetics : EJHG·Aurélie PhamIrène Netchine
Aug 3, 2021·Biochemical Society Transactions·David LlèresRobert Feil
Aug 10, 2021·Frontiers in Cell and Developmental Biology·John Charles RotondoFernanda Martini
Oct 8, 2021·Cold Spring Harbor Molecular Case Studies·Siren BerlandBjørn I Haukanes

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Datasets Mentioned

BETA
KX237564
GSE109408
GM05757

Methods Mentioned

BETA
enzyme-linked immunosorbent assay
genotyping
transfection
RNA-seq
PCA
ELISA
PCR

Software Mentioned

gene set enrichment analysis ( GSEA )
SeqScape
GraphPad
GSEA
GraphPad Prism
IntegraGen

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