title: Human imprinted retrogenes exhibit non-canonical imprint chromatin signatures and reside in non-imprinted host genes.
abstract: Imprinted retrotransposed genes share a common genomic organization including a promoter-associated differentially methylated region (DMR) and a position within the intron of a multi-exonic 'host' gene. In the mouse, at least one transcript of the host gene is also subject to genomic imprinting. Human retrogene orthologues are imprinted and we reveal that human host genes are not imprinted. This coincides with genomic rearrangements that occurred during primate evolution, which increase the separation between the retrogene DMRs and the host genes. To address the mechanisms governing imprinted retrogene expression, histone modifications were assayed at the DMRs. For the mouse retrogenes, the active mark H3K4me2 was associated with the unmethylated paternal allele, while the methylated maternal allele was enriched in repressive marks including H3K9me3 and H4K20me3. Two human retrogenes showed monoallelic enrichment of active, but not of repressive marks suggesting a partial uncoupling of the relationship between DNA methylation and repressive histone methylation, possibly due to the smaller size and lower CpG density of these DMRs. Finally, we show that the genes immediately flanking the host genes in mouse and human are biallelically expressed in a range of tissues, suggesting that these loci are distinct from large imprinted clusters.
authors.affiliation: Imprinting and Cancer Group, Cancer Epigenetics and Biology Program, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, 08907, Barcelona, Spain. dmonk@iconcologia.net
authors.forename: David
authors.initials: D
authors.lastname: Monk
authors.forename: Philippe
authors.initials: P
authors.lastname: Arnaud
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Frost
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wood
authors.forename: Michael
authors.initials: M
authors.lastname: Cowley
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martin-Trujillo
authors.forename: Amy
authors.initials: A
authors.lastname: Guillaumet-Adkins
authors.forename: Isabel
authors.initials: I
authors.lastname: Iglesias Platas
authors.forename: Cristina
authors.initials: C
authors.lastname: Camprubi
authors.forename: Deborah
authors.initials: D
authors.lastname: Bourc'his
authors.forename: Robert
authors.initials: R
authors.lastname: Feil
authors.forename: Gudrun E
authors.initials: GE
authors.lastname: Moore
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Oakey
mesh_terms: D000483:Alleles; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D019175:DNA Methylation; D018392:Genomic Imprinting; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D018626:Retroelements
chemical_list: D002843:Chromatin; D006657:Histones; D018626:Retroelements