Candidate imprinting control regions in dog genome

Abstract

In mammals, genomic imprinting restricts the expression of a subset of genes from one of the two parental alleles. The process is regulated by imprinting control regions (ICRs) dispersed across autosomal chromosomal DNA. An unresolved question is how to discover candidate ICRs across the entire canine genome. Previously, bioinformatics analyses found a significant fraction of well-known ICRs in mouse, human, and Bos taurus. Analyses were based on finding the genomic positions of clusters of several CpG-rich motifs known as ZFBS-morph overlaps. These motifs are composite DNA elements. For this report, we performed similar studies to pinpoint candidate ICRs in the dog genome. A key feature of the bioinformatics approach is creating density plots to mark cluster positions as peaks. In genome-wide analyses, peaks in plots effectively discovered candidate ICRs along chromosomal DNA sequences of the Canis familiaris breed Boxer. With respect to Non-Dog RefSeq Genes, several candidate ICRs are in regions analogous to ICR positions in mouse DNA, in human DNA, or both. In the Boxer genome, examples include candidate ICRs for parent-of-origin-specific expression of the MEST isoform PEG1, INPP5F_V2, the PLAGL1 isoform ZAC1, IGF2R, PEG3, and GNAS loci. In mouse, imprinted genes in these loci play important roles in developmental and physiological processes.

Keywords: Canis familiaris; Allele-specific; Canine; CpG; DMR; Dog genome; Gene regulation; Genome-wide; ICR; Imprinted genes.

Fig. 1

Candidate ICR for allele-specific expression of MEST isoform (PEG1) in the Boxer genome. On the genome browser, genomic landmarks are displayed on horizonal lines known as tracks. A track, colored green, gives the positions of CpG islands in the Boxer genome. A custom track, maroon color, displays peak position in density plots. In hunter green are tracks for viewing the positions of ZFBS-morph overlaps (ZMOs), in pack format, and ZFP57 hexamers in dense format. Tracks in dark blue displays Non-Dog RefSeq Genes. In density-plots, a peak located a candidate ICR in a CpG island (CpG174)

Fig. 2

Candidate ICR for allele-specific expression of PLAGL1 isoform (ZAC1) in the Boxer genome. From top to bottom: the positions of CpG islands, in pack format; density-plot, in full format; ZFBS-morph overlap (ZMOs), in pack format; ZFP57 hexameric sites, in dense format; and Non-Dog RefSeq Genes, in pack format. The candidate ICR is marked by a robust peak in CpG137

Fig. 3

Candidate ICR for allele-specific expression of INPP5F_V2 in the Boxer genome. From top to bottom: the positions of CpG islands; density plot; ZFBS-morph overlaps (ZMOs); ZFP57 hexameric sites; and Non-Dog RefSeq Genes. The candidate ICR is marked by a robust peak in CpG153. In the context of studies of mice and humans, the ICR is intronic and at a correct position

Fig. 4

Candidate ICR for allele specific expression of PEG3/ZIM2 in the Boxer genome. From top to bottom: the positions of CpG islands; density plot; ZFBS-morph overlaps (ZMOs); ZFP57 hexameric sites; and Non-Dog RefSeq Genes. The robust peak marks the candidate ICR location. In the context of studies of humans, candidate ICR position is correct

Fig. 5

Candidate ICR in the GNAS complex locus in the Boxer genome. From top to bottom: the positions of CpG islands; density plot; ZFBS-morph overlaps; ZFP57 binding sites (ZMOs); and Non-Dog RefSeq Genes. The robust peak marks the likely position of a candidate for principal ICR in GNAS complex locus in Boxer

Fig. 6

Candidate ICR for allele specific expression of IGF2R in the Boxer genome. From top to bottom: the positions of CpG islands; density plot; ZFBS-morph overlaps (ZMOs); ZFP57 hexameric sites; and Non-Dog RefSeq Genes. The candidate ICR is intronic and marked by a robust peak

Fig. 7

H19 locus in Boxer genome. From top to bottom: the positions of H19, CpG islands, ZFBS-morph overlaps (ZMOs), and hexameric sequence. Upstream H19, the approach did not find a candidate ICR for regulating allele-specific expression in Boxer DNA. the region includes 3 ZFBS-morph overlaps (ZMOs), and several hexameric site