br Conclusions Histone acetylation deacetylation

Conclusions Histone acetylation/deacetylation is a major epigenetic mechanism implicated in the regulation of transcription and various biological processes such as development and gametogenesis from plants to vertebrates. However, despite being well characterized in zebrafish, acetyltransferase and deacetylase enzymes remain unknown in other fish species, especially patterns of expression during embryogenesis and gametogenesis. Our study provides an important basis for the scientific community interested in understanding these epigenetic mechanisms in other fish species such as the self-fertilizing mangrove rivulus. Our results indicate an evolutionary conservation of the KAT/HDAC enzymes, and mRNA expression patterns suggest biological roles in adult neurogenesis, gametogenesis and embryogenesis consistent with their function in other species. However, as our transcript patterns only reflect an average of expressions, a more detailed analysis of these enzymes is necessary by in situ hybridization, biochemical assays and functional studies (inhibitors or CRISPR-Cas9) to understand precisely their spatial distribution, their biochemical specificities and their biological role in the establishment of a proper Cy5.5 hydrazide state necessary to gamete maturation, information transmission, embryonic development, and possibly behavior. Finally, as a number of rivulus KATs and the Sirtuins were discovered while conducting this study, their expression profiles during the rivulus life cycle should be elucidated together with the regulation of histone acetylation marks. Interactions with other epigenetic mechanisms (e.g., DNA methylation) might permit a more global view of how epigenetic mechanisms are regulated during embryonic development and gametogenesis in the self-fertilizing mangrove rivulus, a valuable new fish model for embryonic development, sex determination and adaptation. The following are the supplementary data related to this article.
Competing interests
Funding This study was supported by the FNRS-FRS (Fonds De La Recherche Scientifique - FNRS) grant No T.0174.14 (Epigenetics in the mangrove rivulus), including a postdoctoral fellowship to A. Fellous. Collection of rivulus lineages was made possible through a permit from the Florida Fish and Wildlife Conservation Commission (Permit #SAL-09-1132B-SR to RLE).
Author contributions
Acknowledgements
Introduction Lysine acetylations are reversible posttranslational modifications that frequently occur on histones and other cellular proteins. These modifications have been recognized to play important regulatory roles in signal transduction cascades and gene expression [1], [2]. Protein lysine acetylations are regulated by histone acetyltransferases (HATs) as writers and histone deacetylases (HDACs) as erasers. In the past decades many different isoforms of HATs and HDACs have been discovered [3], [4], and aberrations in their activity have been associated with diseases such as inflammatory disorders or cancer [5], [6]. For this reason, the development of small molecule inhibitors of these enzymes and their applications in therapeutic areas, such as the treatment of inflammatory diseases, have received considerable attention. This has resulted in the development of small molecule HAT inhibitors (HATi) [7]. Virtual screening enabled the identification of the small molecule inhibitor C646 as a potent and cell-permeable p300 HATi (Ki 0.4μM) which is selective for p300 among HAT isoenzymes such as PCAF, GCN5 and MOZ [8]. C646 has shown interesting effects in disease models. For example, C646 has successfully been applied in an animal model of neuropathic pain. In this study, C646 was administered in rats via a lumbar intrathecal catheter, demonstrating the feasibility of local administration of C646 in animals. It was found that C646 treatment diminished both the p300 promoter binding and the expression of COX-2 [9]. In another study on prostate cancer cell lines it was found that C646 mediated inhibition of p300 increased apoptosis, which was, among others, caused by inhibition of the androgen receptor and the NF-κB pathway [10]. These studies indicate that C646 influences signaling cascades such as the NF-κB pathway.