BADGE As DNA methylation plays a critical role in organismic
As DNA methylation plays a critical role in organismic development and human diseases, the interest in DNA methyltransferases is constantly increasing. Extensive studies on the repertoires of dnmts genes have indicated increasing dnmts members in eukaryotes (Goll and Bestor, 2005; Ponger and Li, 2005). In mammals five dnmts genes have been identified, including dnmt1, dnmt2, dnmt3a, dnmt3b, and dnmt3l (Bestor, 2000). In teleost,such as zebrafish, eight different dnmts genes are identified, including dnmt1, dnmt2, dnmt3aa, dnmt3ab, dnmt3ba, dnmt3bb.1, dnmt3bb.2, and dnmt3bb.3, respectively, based on the nomenclature in ZFIN (http://zfin.org/). The whole genome BADGE (WGD) is considered to be the driving force behind the expansion of gene families. The ancestral genomes of all teleosts underwent two older WGD events (2R) common to all vertebrates (Dehal and Boore, 2005; Van de Peer et al., 2009) and a fish-specific WGD, termed the third round genome duplication (3R) (Meyer and Van, 2005). Some teleosts, like rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio), even underwent a fourth round of genome duplication (4R) (Berthelot et al., 2014; Xu et al., 2014). Recently, genomes of more and more fishes, such as the elephant shark (Callorhinchus milii, a chondrichthyan) (Venkatesh et al., 2014), coelacanth (Latimeria chalumnae, an early sarcopterygian) (Amemiya et al., 2016), spotted gar (Lepisosteus oculatus, a non-teleost actinopterygian) (Amores et al., 2011; Braasch et al., 2016) and common carp (a teleost underwent 4R) (Xu et al., 2014), have been sequenced and published. The available genome sequences of the species mentioned above provide new resources to understand the evolution of dnmts family. In vertebrates, sex of some species is determined either genetically, like in eutherian mammals (Capel, 1998), or environmentally, like in some reptiles (Crews et al., 1994). For most noneutherian vertebrates, sex is affected by both genetic and environmental factors. In fishes, sex determination is flexible. It is influenced by endogenous genetic factors and sensitive to various environmental factors including temperature, steroid hormone, and so on (Devlin and Nagahama, 2002; Nakamura, 2009). Epigenetic mechanisms provide organisms with the ability to modify the activity of their genes in response to changes in the internal or external environment (Jaenisch and Bird, 2003; Piferrer, 2013). It has recently been suggested that the regulation of epigenetic modifications, in particular the methylation of gonads genomic DNA, may play an important role in sex differentiation (Wen et al., 2014). The expression patterns of the dnmts in gonads development and key genes in the sex determination pathways are the major targets of substantial methylation modification (La Salle et al., 2004). The dmrt1 (Doublesex and Mab-3-related transcription factor 1), encoding a sex related transcription factor, has shown a sexual dimorphic expression pattern and its activity is affiliated with testis development (Guo et al., 2005; Li et al., 2013; Marchand et al., 2000). The cyp19a1a (cytochrome P450, family 19, subfamily A, polypeptide 1a), encodes P450 aromatase converting testosterone to 17β-estradiol responsible for estrogen synthesis in fishes (Kobayashi et al., 2003), is also a sexually dimorphic gene and plays an important role in the regulation of ovarian development (Chang et al., 2005; Chiang et al., 2001). Previous studies on various species indicated the changes of DNA methylation patterns of dmrt1 and cyp19a1a can affect sex differentiation (Navarro-Martin et al., 2011; Parrott et al., 2014; Shao et al., 2014; Wu and Chang, 2017; Zhang et al., 2013). In our previous study, 3-month-old female tilapias with differentiated ovaries were successfully induced into functional male by treatment with an aromatase inhibitor, Fadrozole. We named this process as secondary sex reversal (SSR) (Sun et al., 2014). SSR provides an excellent model to elucidate the role of epigenetic modification, and DNA methylation and dnmts may play a crucial role during the process. However, the expression pattern of dnmts during SSR is unclear.