Chromatin remodeling and histones modifying enzymes in bovine oocyte: interpretation of trascriptomic data meets morphology

Before meiotic resumption, the chromatin enclosed within the nucleus of prophase I arrested mammalian oocytes undergoes morphological and functional changes that are crucial for meiotic progression and early embryonic development. Histones post-translational modification such as acetylation and methylation, imposed by histone modifying enzymes, are considered important hallmarks in these processes. However, the study of histone modifications during oogenesis is hindered by the lack of antibodies specific to all the different histone modifications and histones modifiers and by the inaccurateness of protein determination in low-amount samples. Converse-ly, the availability of transcriptomic platforms applicable to oocytes generated, in the last decade, a large amount of data, revealing the expression of histones modifiers. However the interpreta-tion of gene profiling data is not straightforward in oocytes, since in these cells transcripts can be stored for several days before being used for protein synthesis. Hence we propose an integrated experimental and bioinformatics approach to overcome this limitation. Specifically, changes in the transcript levels of histone modifying enzymes coming from different microarray analyses were combined and compared with the corresponding phenotype investigated by immunocyto-chemistry, whenever the antibody specific to the modified histone residue was available. This combined approach enabled the formulation of precise hypotheses on the role of specific en-zymes responsible for histone’s acetylation and methylation signature and it will be expanded to other modifications. This strategy can be particularly useful in large mammalian species that rarely allow the application of genetic manipulation to confirm experimental hypothesis. (Supported by OECD program JA00091594 and NSERC-CRSNG-Canada).