We aimed to explore biomarkers associated with diagnosis and prognosis of colorectal cancer. Differentially expressed protein (DEP) genes were obtained and validated. Moreover, co-expressed genes were screened and their prognostic value was evaluated. In addition, miRNAs that were negatively correlated with DEP genes were identified and used to construct a competitive endogenous RNA network. Furthermore, a support vector machine model was built using DEP genes, and a receiver operating characteristic curve was implemented to confirm its prediction performance. The results showed that only one DEP gene, CCL26, was obtained. Moreover, 43 genes co-expressed with CCL26 were identified, among which six (AP3M2, DAPK1, ISYNA1, PPM1K, PRR4 and RNF122) were linked with the prognosis of colorectal cancer. Besides, the axis RP11-47122.2/RP11-527N22.1–hsa-miR-3192-5p–CCL26 was identified as an lncRNA–miRNA–target gene network. Support vector machine model analysis showed that the area under the curve of CCL26 reached 0.878 based on GEO data and 0.743 based on our protein data. In conclusion, AP3M2, DAPK1, ISYNA1, PPM1K, PRR4, RNF122, CCL26 and hsa-miR-3192-5p appear to be related to the progression of colorectal cancer.

We have previously estimated the evolutionary rate (number of substitutions/site/million years) of mitochondrial cytochrome b gene (Cytb) sequences in rodents and moles to be about 0.11 at more recent divergence times of tens of thousands of years, and to decrease rapidly to about 0.03 at more distant divergence times. Because this time dependency is thought to be caused by the removal of mildly deleterious substitutions in later generations, we focused in this study on the abundance of nonsynonymous substitutions. We collected 23 haplogroups of Cytb with signals of late Quaternary population expansion events from rodents and moles and categorized them into three groups for comparison based on predicted expansion start time: 5,000–15,000 years ago (Group I), ca. 53,000 years ago (Group II) and 130,000–230,000 years ago (Group III). We counted the numbers of nonsynonymous and synonymous substitutions in all haplogroups. The rates of nonsynonymous substitutions were lowest in Groups II and III (0.08–0.22), whereas those in Group I varied markedly. We further classified Group I into two subgroups based on high (0.29–0.43) and low (0.09–0.20) nonsynonymous substitution rates, which were likely to be associated with the start of the expansion within 10,000 years and at around 15,000 years ago, respectively. The Group II and III networks had two- or three-step star-shaped structures and tended to exhibit frequent and less frequent nonsynonymous substitutions on exterior and interior branches, respectively. Based on temporal dynamics, nonsynonymous mitochondrial DNA (mtDNA) substitutions in small mammals accounted for at most 40% of all substitutions during the early evolutionary stage and then rapidly declined, dropping to approximately 15%. The results of this study provide a good explanation of the time-dependent trend in the mtDNA evolution rate predicted in previous work.

Mating-type (P or M) of fission yeast Schizosaccharomyces pombe is determined by the transcriptionally active mat1 cassette and is switched by gene conversion using a donor, either mat2 or mat3, located in an adjacent heterochromatin region (mating-type switching; MTS). In the switching process, heterochromatic donors of genetic information are selected based on the P or M cell type and on the action of two recombination enhancers, SRE2 promoting the use of mat2-P and SRE3 promoting the use of mat3-M, leading to replacement of the content of the expressed mat1 cassette. Recently, we found that the histone H3K4 methyltransferase complex Set1C participates in donor selection, raising the question of how a complex best known for its effects in euchromatin controls recombination in heterochromatin. Here, we report that the histone H2BK119 ubiquitin ligase complex HULC functions with Set1C in MTS, as mutants in the shf1, brl1, brl2 and rad6 genes showed defects similar to Set1C mutants and belonged to the same epistasis group as set1Δ. Moreover, using H3K4R and H2BK119R histone mutants and a Set1-Y897A catalytic mutant, we found that ubiquitylation of histone H2BK119 by HULC and methylation of histone H3K4 by Set1C are functionally coupled in MTS. Cell-type biases in MTS in these mutants suggested that HULC and Set1C inhibit the use of the SRE3 recombination enhancer in M cells, thus favoring SRE2 and mat2-P. Consistent with this, imbalanced switching in the mutants was traced to compromised association of the directionality factor Swi6 with the recombination enhancers in M cells. Based on their known effects at other chromosomal locations, we speculate that HULC and Set1C control nucleosome mobility and strand invasion near the SRE elements. In addition, we uncovered distinct effects of HULC and Set1C on histone H3K9 methylation and gene silencing, consistent with additional functions in the heterochromatic domain.

CpG methylation of genomic DNA is a well-known repressive epigenetic marker in eukaryotic transcription, and DNA methylation of promoter regions is correlated with gene silencing. In contrast to the promoter regions, the function of DNA methylation during transcription termination remains to be elucidated. A recent study revealed that mouse DNA methyltransferase 3a (Dnmt3a) mainly functions in de novo methylation in the promoter and gene body regions, including transcription termination sites (TTSs), during development. To investigate the relationship between DNA methylation overlapping the TTSs and transcription termination, we performed bioinformatics analysis using six pre-existing Dnmt^-/- mouse cell datasets: four types of neurons (three Dnmt3a^-/- and one Dnmt1^-/- mutants) and two types of embryonic fibroblasts (MEFs) (Dnmt3a^-/- and Dnmt3b^-/- mutants). Combined analyses using methylome and transcriptome data revealed that read counts downstream of hypomethylated TTSs were increased in three types of neurons (two Dnmt3a^-/- and one Dnmt1^-/- mutants). Among these, an increase in chimeric transcripts downstream of the TTSs was observed in Dnmt3a^-/- mature olfactory sensory neurons and Dnmt3a^-/- agouti-related peptide (protein)-producing neurons, thereby indicating that read-through occurs in hypomethylated TTSs at specific gene loci in these two mutants. Conversely, in Dnmt3a^-/- MEFs, we detected reductions in read counts downstream of hypomethylated TTSs. These results indicate that the hypomethylation of TTSs can both positively and negatively regulate transcription termination, dependent on Dnmt and cell types. This study is the first to identify the aberrant termination of transcription at specific gene loci with DNA hypomethylated TTSs attributable to Dnmt deficiency.

Understanding the processes and consequences of the morphological diversity of organisms is one of the major goals of evolutionary biology. Studies on the evolution of developmental mechanisms of morphologies, or evo-devo, have been extensively conducted in many taxa and have revealed many interesting phenomena at the molecular level. However, many other taxa exhibiting intriguing morphological diversity remain unexplored in the field of evo-devo. Although the annelid family Syllidae shows spectacular diversity in morphological development associated with reproduction, its evo-devo study, especially on molecular development, has progressed slowly. In this study, we focused on Megasyllis nipponica as a new model species for evo-devo in syllids and performed transcriptome sequencing to develop a massive genetic resource, which will be useful for future molecular studies. From the transcriptome data, we identified candidate genes that are likely involved in morphogenesis, including genes involved in hormone regulation, sex determination and appendage development. Furthermore, a computational analysis of the transcriptome sequence data indicated the occurrence of DNA methylation in coding regions of the M. nipponica genome. In addition, flow cytometry analysis showed that the genome size of M. nipponica was approximately 524 megabases. These results facilitate the study of morphogenesis in molecular terms and contribute to our understanding of the morphological diversity in syllids.