GED: a manually curated comprehensive resource for epigenetic modification of gametogenesis

Briefings in Bioinformatics, 18(1), 2017, 98–104 doi: 10.1093/bib/bbw007 Advance Access Publication Date: 5 February 2016 Paper GED: a manually curated comprehensive resource for epigenetic modification of gametogenesis Corresponding authors. Mingzhi Liao, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China. Tel.: 86 15353735978, Fax.: 86 029 87092262. E-mail: Abstract Reproductive infertility affects seventh of couples, which is most attributed to the obstacle of gametogenesis. Characterizing the epigenetic modification factors involved in gametogenesis is fundamental to understand the molecular mechanisms and to develop treatments for human infertility. Although the genetic factors have been implicated in gametogenesis, no dedicated bioinformatics resource for gametogenesis is available. To elucidate the relationship of epigenetic modification and mammalian gametogenesis, we developed a new database, gametogenesis epigenetic modification database (GED), a manually curated database, which aims at providing a comprehensive resource of epigenetic modification of gametogenesis. The database integrates three kinds information of epigenetic modifications during gametogenesis (DNA methylation, histone modification and RNA regulation), and the gametogenesis has been detailed as 16 stages in seven mammal species (Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa, Bos taurus, Capra hircus and Ovis aries). Besides, we have predicted the linear pathways of epigenetic modification which were composed of 211 genes/proteins and microRNAs that were involved in gametogenesis. GED is a userfriendly Web site, through which users can obtain the comprehensive epigenetic factor information and molecular pathways by visiting our database freely. GED is free available at http://gametsepi.nwsuaflmz.com. Key words: gametogenesis; epigenetic modification; database; pathway; network Introduction As the way of procreation, gametogenesis is an important segment of a mammalian‘s life cycle. Gametogenesis is a complicated process that can be divided into many stages. It starts from the primordial germ cell (PGC). After undergoing the process of mitosis and differentiation, PGCs have eventually developed into mature, functional germ cells. During the development, epigenetic factors play significant roles, Weiyang Bai is a student at the College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China. His research interests include bioinformatics, systems biology and genetics. Wen Yang is a student at the College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China. Her research interests include bioinformatics and systems biology. Wenjing Wang is a student at the College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China. Her research interests include bioinformatics, systems biology and cell biology. Yang Wang is a student at the College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China. His research interests include bioinformatics and systems biology. Can Liu is a student at the College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China. His research interests include bioinformatics, immunology and systems biology. Qinghua Jiang is a professor at the School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150001, China. His research interests include bioinformatics, genetics and systems biology. Jinlian Hua is a professor at the College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi, China. His research interests include reproduction and cell biology. Mingzhi Liao is an associate professor at the College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China. His research interests include bioinformatics and systems biology. Submitted: 23 November 2015; Received (in revised form): 29 December 2015 C The Author 2016. Published by Oxford University Press. For Permissions, please email: V 98 Weiyang Bai, Wen Yang, Wenjing Wang, Yang Wang, Can Liu, Qinghua Jiang, Jinlian Hua and Mingzhi Liao Gametogenesis epigenetic modification database | 99 including DNA methylation, histone modification and noncoding RNA regulation [1, 2]. As an important type of epigenetic modifications, DNA methylation plays an important role in a mammal‘s gametogenesis [3–5]. The status and pattern of DNA methylation as well as DNA methyltransferase dynamically change in gametogenesis according to the cell differentiation state [6–9]. Histone modification is another common type of epigenetic modification in a mammal‘s gametogenesis [10–12], which is involved in diverse biological events, including meiosis interference in large-scale chromatin remodeling, axial chromatid condensation, sister chromatid separation, DNA repair and apoptosis [13–18]. Histone modification also participates in gene expression through histone-modifying enzymes. For example, the H3K4me3 methyltransferase, MLL2, can repress transcription of p53 by trimethylation of H3K4 in oocytes [19]. In addition, in spermatids, the deficiency of JMJD1A, which belongs to H3K9me methyltransferase, will diminish the cyclic adenosine monophosphate-response element modulator [20]. As a posttranscriptional regulation factor, microRNA (miRNA) is essential to the process of gametogenesis in mammals [21–23]. miRNA184 has been found to downregulate nuclear receptor corepressor 2 in mouse spermatogenesis [24]. miRNA21 regulates the self-renewal of mouse spermatogonial stem cells [25]. miRNA221 and miRNA222 maintain the undifferentiated state of mouse spermatogonia by repressing the gene of KIT expression [26]. Moreover, miRNA378 can regulate oocyte maturation by repressing the expression of aromatase in pigs [27]. Additionally, there are interactions among different epigenetic modifications [28], which provides a hint of complex mechanisms about gametogenesis. Although many significant results have been derived from mammal gametogenesis studies, the epigenetic mechanisms controlling this process and pathway are not completely understood. There is a large amount of literature resource that contains fragmented molecular information of epigenetic modification. It is helpful for the study of reproductive development to collect and integrate the related information in these documents about the gametogenesis epigenetic factors and their complex interaction mechanisms. Recently, the epigenetic factors and their complex interactions have been summarized in bioinformatics resource [29, 30]. Even more, some groups have already integrated different kinds of molecular information and tried to identify linear pathways, which will be helpful for the exploration of complex biological systems [31, 32]. These works, however, did not focus on epigenetic factor roles in gametogenesis of mammals. After searching, screening and manual information e (...truncated)