DNA Methylation and HydroxymethylationImprinting and Inheritance

Imprinting, epigenetic markers and assisted reproductive technologies (ARTs)

shutterstock_56038444Epigenetics refers to changes in gene regulation that are do not related to changes in the primary sequence of DNA. It can be reversible and heritable throughout cell division, and its regulation is characterized by several modifications, such as DNA methylation and post-translational changes in the histone proteins. In addition, several proteins and protein complexes interact with the epigenetic factors on the chromatin, participating in gene regulation.

In mammals, a correct DNA methylation reprogramming is essential to gametogenesis and normal embryo development. Imprinted genes, which are essential to embryo development, are expressed in a parent-of-origin-specific manner controlled by allele-specific DNA methylation marks established during gametogenesis. The DNA methylation reprogramming may be susceptible to many environmental factors, such as in vitro culture in assisted reproductive techniques (ARTs).

In embryos-produced by ARTs, morphological evaluation based on the number and compaction of cumulus cells and cytoplasmic homogeneity has been routinely used as a selection criterion for oocyte quality and consequently embryo quality. However, such evaluation alone is not sufficient to identify most competent oocytes.

Considering the essential role of epigenetic reprogramming during gametogenesis and embryogenesis, the identification and use of epigenetic markers during this window of development may be a useful tool to improve ART efficiency and security. In this sense, besides DNA methylation and histone modifications, proteins involved in global chromatin organization are good candidate as molecular markers. Thus, CCCTC-binding factor (CTCF) may be an important candidate molecular marker, due its essential insulator activity, with methylation-sensitive binding sites genome-wide, participating in imprinting establishment and global gene regulation. CTCF associates with a variety of different factors on the chromatin, performing many functions using different partners. Studies evaluating the genome-wide DNA methylation and mutations of CTCF sites and the mutations and expression levels of the CTCF gene are necessary strategies to establish CTCF as a molecular marker.

We are interested in characterizing the methylation patterns that coordinate gametogenesis and early embryonic development in bovine, understanding the adverse effects of the environment on the epigenetic patterns.

Read more about imprinting, epigenetic markers for competent oocytes, and assisted reproductive technologies (ARTs) below!


Related articles:

Franco MM, Prickett AR, & Oakey RJ (2014). The Role of CCCTC-Binding Factor (CTCF) in Genomic Imprinting, Development, and Reproduction. Biology of reproduction PMID: 25297545
Franco MM, Fagundes NS, Michalczechen-Lacerda VA, Caixeta ES, de Castro Rodrigues F, Machado GM, Ferreira AR, & Dode MA (2014). Characterisation of the methylation pattern in the intragenic CpG island of the IGF2 gene in Bos taurus indicus cumulus cells during in vitro maturation. Journal of assisted reproduction and genetics, 31 (1), 115-20 PMID: 24174298

Carvalho JO, Michalczechen-Lacerda VA, Sartori R, Rodrigues FC, Bravim O, Franco MM, & Dode MA (2012). The methylation patterns of the IGF2 and IGF2R genes in bovine spermatozoa are not affected by flow-cytometric sex sorting. Molecular reproduction and development, 79 (2), 77-84 PMID: 22128039

Fagundes NS, Michalczechen-Lacerda VA, Caixeta ES, Machado GM, Rodrigues FC, Melo EO, Dode MA, & Franco MM (2011). Methylation status in the intragenic differentially methylated region of the IGF2 locus in Bos taurus indicus oocytes with different developmental competencies. Molecular human reproduction, 17 (2), 85-91 PMID: 20833870

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Maurício Franco

Maurício Franco

DVM and DSc in Genetics; Researcher, Genetic Resources & Biotechnology Center, EMBRAPA – Brazilian Agricultural Research Corporation, Brasília, Federal District, Brazil.