Abstract
Large-scale transcriptome and methylome data analyses obtained by high-throughput technologies have been enabling the identification of novel imprinted genes. We investigated genome-wide DNA methylation patterns in multiple human tissues, using a high-resolution microarray to uncover hemimethylated CpGs located in promoters overlapping CpG islands, aiming to identify novel candidate imprinted genes. Using our approach, we recovered ~30% of the known human imprinted genes, and a further 168 candidates were identified, 61 of which with at least three hemimethylated CpGs shared by more than two tissue types. Thirty-four of these candidate genes are members of the protocadherin cluster on 5q31.3; in mice, protocadherin genes have non-imprinted random monoallelic expression, which might also be the case in humans. Among the remaining 27 genes, ZNF331 was recently validated as an imprinted gene, and six of them have been reported as candidates, supporting our prediction. Five candidates (CCDC166, ARC, PLEC, TONSL, and VPS28) map to 8q24.3, and might constitute a novel imprinted cluster. Additionally, we performed a comprehensive compilation of known human and mice imprinted genes from literature and databases, and a comparison among high-throughput imprinting studies in humans. The screening for hemimethylated CpGs shared by multiple human tissues, together with the extensive review, appears to be a useful approach to reveal candidate imprinted genes.
Highlights
The appropriate gene expression of each cell type is controlled by several mechanisms, and for most genes, both or neither of the alleles are expressed, depending on the state or identity of a given cell
We investigated the genome-wide DNA methylation pattern of hundreds of thousands of CpG sites in multiple human tissues, using the high-resolution Infinium 450K array platform (HM450K, Illumina, Inc, San Diego, CA, USA)
Most imprinted genes (IG) are conserved between humans and mice; excluding those that have no orthologs between the two species, 62 are specific to mice and only 27 to humans, which may reflect the difficulty in identifying IGs in humans
Summary
The appropriate gene expression of each cell type is controlled by several mechanisms, and for most genes, both or neither of the alleles are expressed, depending on the state or identity of a given cell. Many genes are monoallelically expressed, such as the majority of those on the inactive X chromosome, autosomal genes exhibiting random monoallelic expression, those regulated by polymorphisms in cis-regulatory elements, and imprinted genes (IG) [1]. The most important epigenetic modification at imprinted loci is DNA methylation, that is, the addition of methyl groups in CG dinucleotides, known as CpG sites. Imprinted genes are rich in CpG islands, and acquire methylation according to the parental origin of the allele, leading to differential expression. Two types of differentially methylated regions (DMRs) have been described in imprinting: germline (or primary)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
