The global features of H3K4 and H3K27 trimethylations （H3K4me3 and H3K27me3） have been well studied in recent years, but most of these studies were performed in mammalian cell lines. In this work, we generated the genorne-wide maps of H3K4me3 and H3K27me3 of mouse cerebrum and testis using ChlP-seq and their high-coverage transcriptomes using ribominus RNA-seq with SOLID technology. We examined the global patterns of H3K4me3 and H3K27me3 in both tissues and found that modifications are closely-associated with tissue-specific expression, function and development. Moreover, we revealed that H3K4me3 and H3K27me3 rarely occur in silent genes, which contradicts the findings in previous studies. Finally, we observed that bivalent domains, with both H3K4me3 and H3K27me3, existed ubiquitously in both tissues and demonstrated an invariable preference for the regulation of developmentally-related genes. How- ever, the bivalent domains tend towards a ＂winner-takes-all＂ approach to regulate the expression of associated genes. We also verified the above results in mouse ES cells. As expected, the results in ES cells are consistent with those in cerebrum and testis. In conclusion, we present two very important findings. One is that H3K4me3 and H3K27me3 rarely occur in silent genes. The other is that bivalent domains may adopt a ＂winner-takes-all＂ principle to regulate gene expression.
Although strand-biased gene distribution （SGD） was described some two decades ago, the underlying molecular mechanisms and their relationship remain elusive. Its facets include, but are not limited to, the degree of biases, the strand-preference of genes, and the influence of background nucleotide composition variations. Using a dataset composed of 364 non-redundant bacterial genomes, we sought to illus- trate our current understanding of SGD. First, when we divided the collection of bacterial genomes into non-polC and polC groups according to their possession of DnaE isoforms that correlate closely with taxonomy, the SGD of the polC group stood out more sig- nificantly than that of the non-polC group. Second, when examining horizontal gene transfer, coupled with gene functional conservation （essentiality） and expressivity （level of expression）, we realized that they all contributed to SGD. Third, we further demonstrated a weaker G-dominance on the leading strand of the non-polC group but strong purine dominance （both G and A） on the leading strand of the polC group. We propose that strand-biased nucleotide composition plays a decisive role for SGD since the polC-bearing genomes are not only AT-rich but also have pronounced purine-rich leading strands, and we believe that a special mutation spectrum that leads to a strong purine asymmetry and a strong strand-biased nucleotide composition coupled with functional selections for genes and their functions are both at work.
Mammalian testis development is a complex and highly sophisticated process. To study the dynamic change of normal testis development at the transcriptional level, we investigated mouse testes at three postnatal ages: 6 days postnatal, 4 weeks old, and 10 weeks old, representing infant (PN1), juvenile (PN2), and adult (PN3) stages, respectively. Using ultra high-throughput RNA sequencing (RNA-seq) technology, we obtained 211 million reads with a length of 35 bp. We identified 18837 genes that were expressed in mouse testes, and found that genes expressed at the highest level were involved in spermatogenesis. The gene expression pattern in PN1 was distinct from that in PN2 and PN3, which indicates that spermatogenesis has commenced in PN2. We analyzed a large number of genes related to spermatogenesis and somatic development of the testis, which play important roles at different developmental stages. We also found that the MAPK, Hedgehog, and Wnt signaling pathways were significantly involved at different developmental stages. These findings further our understanding of the molecular mechanisms that regulate testis development. Our study also demonstrates significant advantages of RNA-seq technology for studying transcriptome during development.
GONG WeiPAN LinLinLIN QiangZHOU YuanYuanXIN ChengQiYU XiaoMinCUI PengHU SongNianYU Jun
An organ unique to mammals, the mammary gland develops 90% of its mass after birth and experiences the pregnancy-lactation-involution cycle （PL cycle） during reproduction. To understand mammogenesis at the transcriptomic level and using a ribo-minus RNA-seq protocol, we acquired greater than 50 million reads each for the mouse mammary gland during pregnancy （day 12 of pregnancy）, lactation （day 14 of lactation）, and involution （day 7 of involution）. The pregnancy-, lacta- tion- and involution-related sequencing reads were assembled into 17344, 10160, and 13739 protein-coding transcripts and 1803, 828, and 1288 non-coding RNAs （ncRNAs）, respectively. Differentially expressed genes （DEGs） were defined in the three samples, which comprised 4843 DEGs （749 up-regulated and 4094 down-regulated） from pregnancy to lactation and 4926 DEGs （4706 up-regulated and 220 down-regulated） from lactation to involution. Besides the obvious and substantive up- and down-regulation of the DEGs, we observe that lysosomal enzymes were highly expressed and that their expression coin- cided with milk secretion. Further analysis of transcription factors such as Trpsl, Gtf2i, Tcf712, Nuprl, Vdr, Rbl, and Aebpl, and ncRNAs such as mir-125b, Let7, mir-146a, and mir-15 has enabled us to identify key regulators in mammary gland de- velopment and the PL cycle.
The human pharyngeal microbiome, which resides at the juncture of digestive and respiratory tracts, may have an active role in the prevention of respiratory tract infections, similar to the actions of the intestinal microbiome against enteric infections. Recent studies have demonstrated that the pharyngeal microbiome comprises an abundance of bacterial species that interacts with the local epithelial and immune cells, and together, they form a unique micro-ecological system. Most of the microbial species in microbiomes are obligate symbionts constantly adapting to their unique surroundings. Indigenous commensal species are capable of both maintaining dominance and evoking host immune responses to eliminate invading species. Temporary damage to the pharyngeal microbiome due to the impaired local epithelia is also considered an important predisposing risk factor for infections. Therefore, reinforcement of microbiome homeostasis to prevent invasion of infection-prone species would provide a novel treatment strategy in addition to antibiotic treatment and vaccination. Hence continued research efforts on evaluating probiotic treatment and developing appropriate procedures are necessary to both prevent and treat respiratory infections.
RNA modifications, especially methylation of the N6 position of adenosine （A）--m6A, rep- resent an emerging research frontier in RNA biology. With the rapid development of high-throughput sequencing technology, in-depth study of m6A distribution and function relevance becomes feasible. However, a robust method to effectively identify m6A-modified regions has not been available yet. Here, we present a novel high-efficiency and user-friendly analysis pipeline called MeRIP-PF for the signal identification of MeRIP-Seq data in reference to controls. MeRIP-PF provides a statistical P-value for each identified m6A region based on the difference of read distribution when compared to the con- trols and also calculates false discovery rate （FDR） as a cut offto differentiate reliable m6A regions from the background. Furthermore, MeRIP-PF also achieves gene annotation ofm6A signals or peaks and produce outputs in both XLS and graphical format, which are useful for further study. MeRIP-PF is implemented in Perl and is freely available at http：//software.big.ac.cn/MeRIP-PF.html.
Coat color is an important characteristic of various breeds of domestic animal species.Variation in farm animal coat color is of considerable interest for concealment,communication and protection against solar radiation（Slominski et al.,2004）.It also plays an important role in the regulation of physiological processes（Miyagi and Terai,2013）.
