Characterization of novel paternal ncRNAs at the Plagl1 locus, including Hymai, predicted to interact with regulators of active chromatin.
Genomic imprinting is a complex epigenetic mechanism of transcriptional control that utilizes DNA methylation and histone modifications to bring about parent-of-origin specific monoallelic expression in mammals. Genes subject to imprinting are often organised in clusters associated with large non-coding RNAs (ncRNAs), some of which have cis-regulatory functions. Here we have undertaken a detailed allelic expression analysis of an imprinted domain on mouse proximal chromosome 10 comprising the paternally expressed Plagl1 gene. We identified three novel Plagl1 transcripts, only one of which contains protein-coding exons. In addition, we characterised two unspliced ncRNAs, Hymai, the mouse orthologue of HYMAI, and Plagl1it (Plagl1 intronic transcript), a transcript located in intron 5 of Plagl1. Imprinted expression of these novel ncRNAs requires DNMT3L-mediated maternal DNA methylation, which is also indispensable for establishing the correct chromatin profile at the Plagl1 DMR. Significantly, the two ncRNAs are retained in the nucleus, consistent with a potential regulatory function at the imprinted domain. Analysis with catRAPID, a protein-ncRNA association prediction algorithm, suggests that Hymai and Plagl1it RNAs both have potentially high affinity for Trithorax chromatin regulators. The two ncRNAs could therefore help to protect the paternal allele from DNA methylation by attracting Trithorax proteins that mediate H3 lysine-4 methylation.
Servicio de Neonatología, Hospital Sant Joan de Déu, Fundació Sant Joan de Déu, Barcelona, Spain.
Isabel
I
Iglesias-Platas
Alex
A
Martin-Trujillo
Davide
D
Cirillo
Franck
F
Court
Amy
A
Guillaumet-Adkins
Cristina
C
Camprubi
Deborah
D
Bourc'his
Kenichiro
K
Hata
Robert
R
Feil
Gian
G
Tartaglia
Philippe
P
Arnaud
David
D
Monk
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D018392:Genomic Imprinting; D051379:Mice; D008969:Molecular Sequence Data; D059368:RNA Isoforms; D020871:RNA Stability; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics*; D022661:RNA, Untranslated / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C509782:HYMAI, RNA; C498423:Plagl1 protein, mouse; D059368:RNA Isoforms; D012333:RNA, Messenger; D022661:RNA, Untranslated; D014157:Transcription Factors; C498796:Dnmt3l protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases