Genomic Imprinting at the Porcine DIRAS3 Locus

Ahn, Jinsoo; Hwang, In-Sul; Park, Mi-Ryung; Hwang, Seongsoo; Lee, Kichoon

doi:10.3390/ani11051315

Cited by 4 publications

(4 citation statements)

References 31 publications

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“…For analyses of bulk RNA-sequencing (RNA-seq), raw data were retrieved from public databases and processing was performed as described previously in our report ( Ahn et al, 2021 ). In detail, the raw FASTQ files were checked with FastQC v0.11.7 and then adapter-trimmed and filtered by Trimmomatic v0.38 with default parameters ( Bolger et al, 2014 ).…”

Section: Methodsmentioning

confidence: 99%

A novel testis-enriched gene, Samd4a, regulates spermatogenesis as a spermatid-specific factor

Ahn

Kim

Park

et al. 2022

Front. Cell Dev. Biol.

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Spermatogenesis is the highly orchestrated process involving expression of a series of testicular genes. Testis-enriched genes are critical for cellular processes during spermatogenesis whose disruption leads to impaired spermatogenesis and male infertility. Nevertheless, among poorly investigated testicular genes are the mouse Samd4a and human SAMD4A which were identified in the current study as novel testis-enriched genes through transcriptomic analyses. In particular, as orthologous alternative splicing isoforms, mouse Samd4a E-form and human SAMD4AC-form containing the SAM domain were specific to testes. Western blot analyses revealed that the murine SAMD4AE-form was predominantly found in the testis. Analyses on GEO2R and single-cell RNA-seq datasets revealed that the Samd4a/SAMD4A expression was enriched in spermatids among various types of cells in adult testes. To investigate in vivo functions of Samd4a, Samd4a knockout mice were generated using the CRISPR/Cas9 system. The Samd4a deficiency resulted in lower testis weight, absence of elongated spermatids, and an increased number of apoptotic cells. Profiling of gene expression in human testis samples revealed that the SAMD4A expression was comparable between obstructive azoospermia patients and normal controls, but significantly lowered in nonobstructive azoospermia (NOA) patients. Among three subgroups of NOA, pre-meiotic arrest (NOA-pre), meiotic arrest (NOA-mei), and post-meiotic arrest (NOA-post), expression level of SAMD4A was higher in the NOA-post than the NOA-mei, but there was no difference between the NOA-pre and NOA-mei. The current studies demonstrated spermatid stage-specific expression of Samd4a/SAMD4A, and impairment of the late stages of spermatogenesis by disruption of the mouse Samd4a gene. These data suggest that Samd4a/SAMD4A plays an essential role in normal spermatogenesis, and SAMD4A, as a spermatid specific marker, can be used for subcategorizing NOA patients. Further understanding the molecular role of SAMD4A will advance our knowledge on genetic regulations in male infertility.

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Section: Methodsmentioning

confidence: 99%

A novel testis-enriched gene, Samd4a, regulates spermatogenesis as a spermatid-specific factor

Ahn

Kim

Park

et al. 2022

Front. Cell Dev. Biol.

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“…Further examples of imprinted genes associated with male infertility include GNAS and the tumor suppressor DIRAS3, although the disruption of methylation patterns in correlation with fertility remains unclear (Tang et al, 2018). Whole-genome bisulfite sequencing (WGBS) and RNA-sequencing approaches in porcine embryos facilitate the identification of imprinted genes, where DIRAS3 is maternally imprinted in the embryo and remains hypermethylated in other tissues including the hypothalamus (Ahn et al, 2021). The regulation of DIRAS3 and other imprinted genes in the early embryo has not been fully elucidated, and comprehensive mechanisms are beyond the scope of this review.…”

Section: Control Of Imprinted Genesmentioning

confidence: 99%

Insights to maternal regulation of the paternal genome in mammalian livestock embryos: A mini-review

Daigneault

2022

Front. Genet.

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This mini-review focuses on current knowledge regarding maternal regulation of the paternal genome in early embryos of mammalian livestock species. Emphasis has been placed on regulatory events described for maternally imprinted genes and further highlights transcriptional regulation of the post-fertilization paternal genome by maternal factors. Specifically, the included content aims to summarize genomic and epigenomic contributions of paternally expressed genes, their regulation by the maternal embryo environment, and chromatin structure that are indispensable for early embryo development. The accumulation of current knowledge will summarize conserved allelic function among species to include molecular and genomic studies across large domestic animals and humans with reference to founding experimental animal models.

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“…However, although imprinted genes have been identified first in mice and humans in most cases and a subset of orthologous loci is imprinted in domesticated animals [ 11 ], there can be livestock-specific imprinting that has not been investigated. Our recent approach of the use of whole-genome bisulfite sequencing (WGBS) and RNA sequencing (RNA-seq) of porcine embryos that underwent parthenogenesis has facilitated verification of imprinting status of gene clusters [ 9 , 12 ]. This facilitation was attributed to a direct sequencing comparison between parthenogenetic and biparental porcine embryos.…”

Section: Introductionmentioning

confidence: 99%

Imprinting at the KBTBD6 locus involves species-specific maternal methylation and monoallelic expression in livestock animals

Ahn,

Hwang,

Park

et al. 2023

J Animal Sci Biotechnol

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Background The primary differentially methylated regions (DMRs) which are maternally hypermethylated serve as imprinting control regions (ICRs) that drive monoallelic gene expression, and these ICRs have been investigated due to their implications in mammalian development. Although a subset of genes has been identified as imprinted, in-depth comparative approach needs to be developed for identification of species-specific imprinted genes. Here, we examined DNA methylation status and allelic expression at the KBTBD6 locus across species and tissues and explored potential mechanisms of imprinting. Results Using whole-genome bisulfite sequencing and RNA-sequencing on parthenogenetic and normal porcine embryos, we identified a maternally hypermethylated DMR between the embryos at the KBTBD6 promoter CpG island and paternal monoallelic expression of KBTBD6. Also, in analyzed domesticated mammals but not in humans, non-human primates and mice, the KBTBD6 promoter CpG islands were methylated in oocytes and/or allelically methylated in tissues, and monoallelic KBTBD6 expression was observed, indicating livestock-specific imprinting. Further analysis revealed that these CpG islands were embedded within transcripts in porcine and bovine oocytes which coexisted with an active transcription mark and DNA methylation, implying the presence of transcription-dependent imprinting. Conclusions In this study, our comparative approach revealed an imprinted expression of the KBTBD6 gene in domesticated mammals, but not in humans, non-human primates, and mice which implicates species-specific evolution of genomic imprinting.

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Genomic Imprinting at the Porcine DIRAS3 Locus

Cited by 4 publications

References 31 publications

A novel testis-enriched gene, Samd4a, regulates spermatogenesis as a spermatid-specific factor

A novel testis-enriched gene, Samd4a, regulates spermatogenesis as a spermatid-specific factor

Insights to maternal regulation of the paternal genome in mammalian livestock embryos: A mini-review

Imprinting at the KBTBD6 locus involves species-specific maternal methylation and monoallelic expression in livestock animals

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