br Introduction Regulation of transcription is a critical

Introduction Regulation of transcription is a critical event of the embryonic development and epigenetic mechanisms such as histone modifications and DNA methylation appear important in mediating temporal changes, and differences among cells/tissues, of temporary stabilized transcriptomes (Mas et al., 2011; Meissner, 2010). It is now widely demonstrated that compaction of chromatin, and therefore transcriptional activity of the concerned genomic regions, is influenced by histone marks (Cervera et al., 2009). These marks are associated either with inactive regions or heterochromatin, where DNA is more compact and consequently less accessible for transcription, or to active regions or euchromatin, where DNA is accessible to the transcriptional machinery (Chen et al., 2016). Acetylation of histone lysine residues is one of the most studied of the histone marks, and plays important roles in the control of gene expression, chromatin assembly, cell reprogramming, 11-dUTP progression and DNA repair in embryo, gametes and adult life stages (Sheikh & Akhtar, 2018; Shin et al., 2018; Sterner & Berger, 2000). Lysine acetyltransferases (KATs), which add acetyl groups to lysine residues, and lysine histone deacetylases (HDACs), which remove the acetyl groups, are the key enzymes regulating acetylation of histone tails (Roth et al., 2001). Histone acetyltransferases (HATs), recently renamed as KAT enzymes to reflect the diversity of their protein substrates (Allis et al., 2007), have been classified into two types based on domain organization and protein sequence. Nuclear type A uses nucleosomal histones only, whereas type B uses non-nucleosomal histones associated with a partial cytoplasmic localization (Brownell & Allis, 1996). Type B KATs include five distinct multi-gene families: GNAT (GCN5-related N-acetyltransferase), MYST (Myst 1, Myst2, Myst3 and Myst4), P300/CBP (CREB-binding protein), basal transcription factor/nuclear receptor cofactors (sometimes including clock) and Camello (Karmodiya et al., 2014; Roth et al., 2001). On the other hand, Histone deacetylase enzymes (HDAC) regulate histone deacetylation. Evolutionary conserved among organisms, they are classified into two families: SIR2/Sirtuin and “classical” HDAC (de Ruijter et al., 2003). SIR2/Sirtuin exhibit a highly conserved catalytic domain and represent a distinct group of NAD+ dependent enzymes (Greiss & Gartner, 2013; Seto & Yoshida, 2014), while members of the “classical” HDAC family are zinc-dependent hydrolases that can be divided into three groups: Class I (HDAC 1, 2, 3 and 8), Class II (HDAC 4, 5, 6, 7, 9 and 10) and Class IV (HDAC 11) (Greiss & Gartner, 2013; Seto & Yoshida, 2014). Despite being very important in various cellular, reproductive and developmental processes in mice and zebrafish (Lee et al., 2015; Urvalek & Gudas, 2014; Xu et al., 2000; Yin et al., 2017), and to be involved in neurodegenerative diseases (Tago & Toyohara, 2018) and depressive disorders (Sowa-ku et al., 2017) in humans, the precise roles of each KAT/HDAC are largely unknown (Karmodiya et al., 2014; Yamaguchi et al., 2005). Furthermore, whereas fish are already widely used as model organisms in developmental, reproductive and environmental studies, most of our understanding of epigenetic regulation of fish gametogenesis and embryology has come from few species (mainly medaka and zebrafish) (Best et al., 2018; Labbé et al., 2017); and, to our knowledge, characterization of these fundamental proteins in histone modifications has focused only on zebrafish (He et al., 2014; Ignatius et al., 2013; Karmodiya et al., 2014; Yamaguchi et al., 2005). Here, we investigated putative KAT/HDAC in a killifish species, the mangrove rivulus (Kryptolebias marmoratus, hereafter ‘rivulus’), which is closely associated with highly variable red mangrove (Rhizophora mangle) ecosystems in Florida, the Bahamas, Central America, and Brazil (Avise & Tatarenkov, 2015; Tatarenkov et al., 2011; Taylor, 2000). Living in microhabitats that exclude most other fish species such as ephemeral pools, crab burrows or even sometimes inside rotting logs, rivulus exhibit many anatomical, physiological, and behavioral adaptations that allow them to inhabit environments with very low dissolved oxygen, high levels of hydrogen sulphide and extreme temperatures (Taylor, 2012). This species is also exceptional as the only known self-fertilizing hermaphroditic vertebrate together with its sister species, K. hermaphroditus (; ). Wild populations of rivulus are composed of a majority of hermaphrodites that coexist with a low proportion of males (up to 5% in Florida) (Furness et al., 2015; Mackiewicz et al., 2006b; Mackiewicz et al., 2006c) and constitute a rare androdioecious mixed mating system where many homozygous and heterozygous individuals exist within and among populations (Avise & Tatarenkov, 2012; Mackiewicz et al., 2006c). In nature, many generations of exclusive selfing gives rise to natural isogenic strains (Mackiewicz et al., 2006a; Tatarenkov et al., 2012), while outcrossing with males (and resulting heterozygosity) is possible due to the capacity of hermaphrodites to lay unfertilized eggs (Mackiewicz et al., 2006a). Moreover, remarkable levels of developmental plasticity have been demonstrated ((Taylor, 2000);, (Mesak et al., 2015; Wells et al., 2015)) in life history (sexual phenotype, growth rates (Lin et al., 1999), and fecundity) and morphological traits (Harrington & Crossman, 1976) within isogenic lineages, and also among lineages/populations (Earley et al., 2012; Grageda et al., 2005). Indeed, adult hermaphrodites undergo sex change to become secondary males, and rivulus embryos that experience low temperature (18 °C) may develop directly as primary males (Earley et al., 2012; Harrington, 1961). Furthermore, it has been hypothesized that epigenetic regulation of the sex ratio, via DNA methylation, might explain natural variation among populations in the extent of selfing versus outcrossing (Ellison et al., 2015), and a very long, deep and late reprogramming DNA methylation event has been demonstrated in this species (Fellous et al., 2018). Knowing that DNA methylation reprogramming represents a highly critical window sensitive to environmental stress in zebrafish (Dorts et al., 2016; Martin et al., 1999), it may represent an opportunity for rivulus embryos living in a highly variable environment to integrate environmental cues at the epigenetic level (Fellous et al., 2018). Unique compare to other described vertebrates; this reprogramming event highlighted the importance to elucidate epigenetic mechanisms in this species, and more generally in teleost fishes.