Discovering candidate imprinted genes and imprinting control regions in the human genome

Bina, Minou

doi:10.1186/s12864-020-6688-8

Cited by 10 publications

(22 citation statements)

References 70 publications

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“…Furthermore –as previously demonstrated for human and mouse [ 40 , 41 ]– peaks in plots of entire chromosomal DNA predicted ICRs for many candidates imprinted genes in Bos taurus (Fig. 11 ).…”

Section: Resultssupporting

confidence: 77%

“…Therefore, it seems likely that ZAC1 corresponds to the transcript annotated as PLAGL1 in cattle RefSeq Genes. In that context, the peak in cattle DNA is intragenic –as observed in human genomic DNA [ 41 ]. Hence, we are tempted to conclude that our strategy has pinpointed the reported putative ZAC1 DMR [ 61 ], and to deduce that in cattle PLAGL1 locus , the putative ZAC1 DMR is a bona fide ICR (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Along the Bos taurus genome, uncover candidate imprinting control regions

2022

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Background In mammals, Imprinting Control Regions (ICRs) regulate a subset of genes in a parent-of-origin-specific manner. In both human and mouse, previous studies identified a set of CpG-rich motifs occurring as clusters in ICRs and germline Differentially Methylated Regions (gDMRs). These motifs consist of the ZFP57 binding site (ZFBS) overlapping a subset of MLL binding units known as MLL morphemes. MLL or MLL1 (Mixed Lineage Leukemia 1) is a relatively large multidomain protein that plays a central role in the regulation of transcription. The structures of both MLL1 and MLL2 include a domain (MT) that binds CpG-rich DNA and a conserved domain (SET) that methylates lysine 4 in histone H3 producing H3K4me3 marks in chromatin. Results Since genomic imprinting impacts many developmental and key physiological processes, we followed a previous bioinformatics strategy to pinpoint ICR positions in the Bos taurus genome. Initial genome-wide analyses involved finding the positions of ZFP57 binding sites, and the CpG-rich motifs (ZFBS-morph overlaps) along cattle chromosomal DNA. By creating plots displaying the density of ZFBS-morph overlaps, we removed background noise and thus improved signal detection. With the density-plots, we could view the positions of peaks locating known and candidate ICRs in cattle DNA. Our evaluations revealed the correspondence of peaks in plots to reported known and inferred ICRs/DMRs in cattle. Beside peaks pinpointing such ICRs, the density-plots also revealed additional peaks. Since evaluations validated the robustness of our approach, we inferred that the additional peaks may correspond to candidate ICRs for imprinted gene expression. Conclusion Our bioinformatics strategy offers the first genome-wide approach for systematically localizing candidate ICRs. Furthermore, we have tailored our datasets for upload onto the UCSC genome browser so that researchers could find known and candidate ICRs with respect to a wide variety of annotations at all scales: from the positions of Single Nucleotide Polymorphisms (SNPs), to positions of genes, transcripts, and repeated DNA elements. Furthermore, the UCSC genome browser offers tools to produce enlarged views: to uncover the genes in the vicinity of candidate ICRs and thus discover potential imprinted genes for experimental validations.

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Section: Resultssupporting

confidence: 77%

Section: Resultsmentioning

confidence: 99%

Along the Bos taurus genome, uncover candidate imprinting control regions

2022

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“…Although not completely confirmed, PRDM8 is considered as a candidate of imprinted genes and the predicted ICR in human located in its last exon 47,48 . The gene structure of PRDM8 is highly conserved between human and bovine, thus this DMR overlapped CpG island is not likely to be the ICR 48 . Accordingly, PRDM8 was not found to be misregulated in fibroblast cells nor in muscle of ART-LOS fetuses 18,23 .…”

Section: Discussionmentioning

confidence: 99%

Spontaneous and ART-induced large offspring syndrome: similarities and differences in DNA methylome

Lopes

Coy

et al. 2022

Preprint

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Large/abnormal offspring syndrome (LOS/AOS) is a congenital overgrowth syndrome reported in ruminants produced by assisted reproduction (ART-LOS) which exhibit global disruption of the epigenome and transcriptome. LOS/AOS shares phenotypes and epigenotypes with the human congenital overgrowth condition Beckwith-Wiedemann syndrome. We have reported that LOS occurs spontaneously (SLOS), however, to date, no study has been conducted to determine if SLOS has the same methylome epimutations as ART-LOS. In this study, we performed whole genome bisulfite sequencing to examine global DNA methylation in SLOS and ART-LOS tissues. We observed unique patterns of global distribution of differentially methylated regions (DMRs) over different genomic contexts, such as promoters, CpG islands and surrounding regions, and repetitive sequences from different treatment groups. In addition, we identified hundreds of LOS-vulnerable DMRs across different cattle breeds when analyzing four idependent LOS experiments together. Specifically, there are 25 highly vulnerable DMRs that could potentially serve as molecular markers for the diagnosis of LOS, including at the promoters of DMRT2 and TBX18, at the imprinted gene bodies of IGF2R, PRDM8, and BLCAP/NNAT, and at multiple CpG islands. We also observed tissue-specific DNA methylation patterns between muscle and blood, and conservation of ART-induced DNA methylation changes between muscle and blood. We conclude that as in ART-LOS, alterations of the epigenome are involved in the etiology of SLOS. In addition, SLOS and ART-LOS share some similarities in methylome epimutations.

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“…For studies of genomic imprinting in cattle, we followed a previous approach applied to mouse and human genomic DNA [26,27]. Briefly: at the UCSC genome browser, we retrieved the DNA sequences of each cattle chromosome (reported for the build bosTau8).…”

Section: Resultsmentioning

confidence: 99%

“…In both mouse and human DNA, known ICRs/gDMRs encompassed clusters of two or more ZFBS-morph overlaps [26,27]. Therefore, we wished to investigate whether known bovine ICRs also included these composite-DNA-elements for regulating parent-of-origin-specific expression.…”

Section: Introductionmentioning

confidence: 99%

Along the Bos Taurus genome, uncover candidate Imprinting Control Regions

Wyss

Song

Bina

2021

Preprint

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In mammals, Imprinting Control Regions (ICRs) regulate a subset of genes in a parent-of-origin-specific manner. In both human and mouse, previous studies identified a set of CpG-rich motifs that occurred as clusters in ICRs and germline Differentially Methylated Regions (gDMRs). These motifs consist of the ZFP57 binding site (ZFBS) overlapping a subset of MLL binding units known as MLL morphemes. Furthermore, by creating plots for displaying the density of these overlaps, it became possible to locate known and candidate ICRs in mouse and human genomic DNA. Since genomic imprinting impacts many developmental and key physiological processes, we performed genome-wide analyses to create plots displaying the density of the CpG-rich motifs (ZFBS-morph overlaps) along Bos Taurus chromosomal DNA. We tailored our datasets so that they could be displayed on the UCSC genome browser (the build bosTau8). On the genome browser, we could view the ZFP57 binding sites, the ZFBS-morph overlaps, and peaks in the density-plots in the context of cattle RefSeq Genes, Non-Cow RefSeq Genes, CpG islands, and Single nucleotide polymorphisms (SNPs). Our datasets revealed the correspondence of peaks in plots to known and deduced ICRs in Bos Taurus genomic DNA. We illustrate that by uploading our datasets onto the UCSC genome browser, we could discover candidate ICRs in cattle DNA. In enlarged views, we could pinpoint the genes in the vicinity of candidate ICRs and thus discover potential imprinted genes.

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Discovering candidate imprinted genes and imprinting control regions in the human genome

Cited by 10 publications

References 70 publications

Along the Bos taurus genome, uncover candidate imprinting control regions

Along the Bos taurus genome, uncover candidate imprinting control regions

Spontaneous and ART-induced large offspring syndrome: similarities and differences in DNA methylome

Along the Bos Taurus genome, uncover candidate Imprinting Control Regions

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