Simultaneous discovery of candidate imprinted genes and Imprinting Control Regions in the mouse genome

Bina, Minou; Wyss, Phillip

doi:10.1101/780551

Cited by 4 publications

(15 citation statements)

References 92 publications

(172 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To evaluate the power of our strategy, we have closely inspected peak positions in genomic sequences reported for mouse, human, and Bos taurus (Table 1). In addition to previously published reports [26,40,41], we have also checked peak positions with respect to experimental data reported in GEO series GSE77444. Briefly, the experimental approach was to use mouse embryonic stem cells (ESCs) E14 to locate regions associated with ZFP57, KAP1, and H3K9me3 marks in chromatin [25].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Along the Bos taurus genome, uncover candidate imprinting control regions

2022

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

“…In both mouse and human DNA, known ICRs/gDMRs encompass clusters of two or more ZFBS-morph overlaps [40,41]. Therefore, we wished to investigate whether known or inferred cattle ICRs/DMRs also included these composite-DNA-elements for regulating parentof-origin-specific expression.…”

Section: Introductionmentioning

confidence: 99%

Along the Bos taurus genome, uncover candidate imprinting control regions

2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…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%

“…Overall, robustness of peaks depends on the number of ZFBS-morph overlaps they encompass. Peaks that cover 2 ZFBS-morph overlaps could be true or false positive [26]. Peaks that cover 3 are more robust.…”

Section: Within Bos Taurus Chromosome 13 An Intragenic Peak Located the Icr Regulating Allele-specific Expression Of Nnatmentioning

confidence: 99%

See 1 more Smart Citation

Along the Bos Taurus genome, uncover candidate Imprinting Control Regions

Wyss

Song

Bina

2021

Preprint

Self Cite

View full text Add to dashboard Cite

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.

show abstract

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

Bina

2020

BMC Genomics

View full text Add to dashboard Cite

Background Genomic imprinting is a process thereby a subset of genes is expressed in a parent-of-origin specific manner. This evolutionary novelty is restricted to mammals and controlled by genomic DNA segments known as Imprinting Control Regions (ICRs) and germline Differentially Methylated Regions (gDMRs). Previously, I showed that in the mouse genome, the fully characterized ICRs/gDMRs often includes clusters of 2 or more of a set of composite-DNA-elements known as ZFBS-morph overlaps. Results Because of the importance of the ICRs to regulating parent-of-origin specific gene expression, I developed a genome-wide strategy for predicting their positions in the human genome. My strategy consists of creating plots to display the density of ZFBS-morph overlaps along the entire chromosomal DNA sequences. In initial evaluations, I found that peaks in these plots pinpointed several of the known ICRs/gDMRs along the DNA in chromosomal bands. I deduced that in density-plots, robust peaks corresponded to actual or candidate ICRs in the DNA. By locating the genes in the vicinity of candidate ICRs, I could discover potential imprinting genes. Additionally, my assessments revealed a connection between several of the potential imprinted genes and human developmental anomalies. Examples include Leber congenital amaurosis 11, Coffin-Siris syndrome, progressive myoclonic epilepsy-10, microcephalic osteodysplastic primordial dwarfism type II, and microphthalmia, cleft lip and palate, and agenesis of the corpus callosum. Conclusion With plots displaying the density of ZFBS-morph overlaps, researchers could locate candidate ICRs and imprinted genes. Since the datafiles are available for download and display at the UCSC genome browser, it is possible to examine the plots in the context of Single nucleotide polymorphisms (SNPs) to design experiments to discover novel ICRs and imprinted genes in the human genome.

show abstract

Simultaneous discovery of candidate imprinted genes and Imprinting Control Regions in the mouse genome

Cited by 4 publications

References 92 publications

Along the Bos taurus genome, uncover candidate imprinting control regions

Along the Bos taurus genome, uncover candidate imprinting control regions

Along the Bos Taurus genome, uncover candidate Imprinting Control Regions

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

Contact Info

Product

Resources

About