• The importance of assessing DNA methylation in genomic imprinting
  • Mohaddeseh Ranjbari,1,* , Seyed Ali Sadat,2 Amir Ali Haj Rajabali Tehrani‌,3
    1. Bachelor of Microbiology, Faculty of New Sciences, Islamic Azad University of Medical Sciences, Tehran, Iran
    2. Department of Biomedical Engineering, Faculty of New Sciences and Technologies, Islamic Azad University, Science and Research Branch, Tehran, Iran
    3. Department of Biomedical Engineering, Faculty of New Sciences and Technologies, Islamic Azad University, Science and Research Branch, Tehran, Iran


  • Introduction: Genomic imprinting is the process of gene silencing through DNA methylation at imprint control regions (ICRs), which is established in embryonic gametes. DNA methylation has a dual role: it can act both as an imprinting mark and as a repressor of gene expression. These modifications include 5 methylcytosine and 5-hydroxymethylcytosine. Clusters of imprinted genes are usually controlled by an imprint center, the )ICR(, which is necessary for allele-specific expression and reprograms parental information across generations. Furthermore, )CpG( methylation regulates gene expression through the recruitment of repressor proteins and histone modifications
  • Methods: In this research, various articles were reviewed using online databases such as Google Scholar and the journal Nature Reviews Genetics, focusing on topics including imprinting control regions (ICRs) of genes through one of two mechanisms: insulator-mediated repression via CTCF or transcription of non coding RNAs, as well as specific promoters and CTCF binding sites. Additionally, maternal allele ICRs during oocyte growth and clusters of imprinted genes that affect phenotype were examined. Finally, the stabilization of gamete imprinting after their lifespan was investigated to achieve appropriate expression patterns in the zygote and embryo
  • Results: Various studies have shown that methylation at KvDMR1 remains unchanged in mutant mice, and targeted mutation does not affect the function of the Kcnq1ot1 promoter. It has been revealed that the enzyme TET3 likely plays a role in the demethylation of the paternal genome in the pre-implantation embryo, and most imprinting control regions (ICRs) are methylated on the maternal allele during oocyte growth. Considering that DNA methylation patterns at ICRs differ depending on parental origin, most ICRs rely on DNMT3A and DNMT3L enzymes for methylation. According to studies, parent-of-origin-specific methylation at CpG sites is established during gametogenesis, and its deficiency is associated with impaired expression of imprinted genes. Furthermore, the maintenance of imprinting after fertilization requires the cooperation of both cis- and trans-acting factors to escape genomic reprogramming
  • Conclusion: Research findings indicate that maternal and paternal imprinting control regions (ICRs) exhibit distinct patterns of histone methylation and transcription in male germline cells during imprint acquisition. The enzyme TET3 is likely involved in the demethylation of the paternal genome in the pre-implantation embryo; however, its deletion leads to reduced fertility. Studies have demonstrated a strong correlation between maternal ICRs, promoter activity, histone H3 lysine-4 methylation, and protection against DNA methylation. On the paternal allele, since most ICRs depend on DNMT3A and DNMT3L enzymes for methylation, DNA methylation in male gametes prevents CTCF binding to ICRs. Additionally, the critical role of DNA methylation in genomic imprinting has been confirmed through Dnmt1 deletion experiments and environmental influences. Moreover, alterations related to intrauterine growth restriction (IUGR) have been observed in the methylation patterns and expression of imprinted genes. Nevertheless, how methylation marks are maintained against genome-wide reprogramming after fertilization remains one of the most important and key questions in the field of genomic imprinting, as this issue defines how parent specific methylation is preserved from erasure and resetting
  • Keywords: Genomic Imprinting , Methylation , DNA Methylation