Influenza B virus hemagglutinin (HA) is a major surface glycoprotein with frequent amino acid substitutions. However, the roles of antibody selection in the amino acid substitutions of HA were still poorly understood. In order to gain insights into this important issue, an analysis was conducted on a total of 271 HA 1 sequences of influenza B virus strains isolated during . In this analysis, phylogenetic analysis by maximum likelihood (PAML) package was used to detect the existence of positive selection and to identify positively selected sites on HA 1 . Strikingly, all the positively selected sites were located in the four major epitopes (120-loop, 150-loop, 160-loop, and 190-helix) of HA identified in previous studies, thus supporting a predominant role of antibody selection in HA evolution. Of particular significance is the involvement of the 120-loop in positive selection, which may become increasingly important in future field isolates. Despite the absence of different subtypes, influenza B virus HA continued to evolve into new sublineages, within which the four major epitopes were targeted selectively in positive selection. Thus, any newly emerging strains need to be placed in the context of their evolutionary history in order to understand and predict their epidemic potential.

As key epigenetic regulators, polycomb group (PcG) proteins are responsible for the control of cell proliferation and differentiation as well as stem cell pluripotency and self-renewal. Aberrant epigenetic modification by PcG is strongly correlated with the severity and invasiveness of many types of cancers. Unfortunately, the molecular mechanism of PcG-mediated epigenetic regulation remained elusive, partly due to the extremely limited pool of experimentally confirmed PcG target genes. In order to facilitate experimental identification of PcG target genes, here we propose a novel computational method, EpiPredictor, that achieved significantly higher matching ratios with several recent chromatin immunoprecipitation studies than jPREdictor, an existing computational method. We further validated a subset of genes that were uniquely predicted by EpiPredictor by cross-referencing existing literature and by experimental means. Our data suggest that multiple transcription factor networking at the cis-regulatory elements is critical for PcG recruitment, while high GC content and high conservation level are also important features of PcG target genes. EpiPredictor should substantially expedite experimental discovery of PcG target genes by providing an effective initial screening tool. From a computational standpoint, our strategy of modelling transcription factor interaction with a non-linear kernel is original, effective and transferable to many other applications.

Polycomb group (PcG) and Trithorax group (TrxG) proteins are essential for maintaining epigenetic memory in both embryonic stem cells and differentiated cells. To date, how they are localized to hundreds of specific target genes within a vertebrate genome had remained elusive. Here, by focusing on short cis-acting DNA elements of single functions, we discovered three classes of response elements in human genome: Polycomb response elements (PREs), Trithorax response elements (TREs) and Polycomb/Trithorax response elements (P/TREs). In particular, the four PREs (PRE14, 29, 39 and 48) are the first set of, to our knowledge, bona fide vertebrate PREs ever discovered, while many previously reported Drosophila or vertebrate PREs are likely P/TREs. We further demonstrated that YY1 and CpG islands are specifically enriched in the four TREs (PRE30, 41, 44 and 55), but not in the PREs. The three classes of response elements as unraveled in this study should guide further global investigation and open new doors for a deeper understanding of PcG and TrxG mechanisms in vertebrates.

Polycomb group (PcG) and trithorax group (TrxG) proteins are essential for maintaining epigenetic memory in both embryonic stem cells and differentiated cells. To date, how they are localized to hundreds of specific target genes within a vertebrate genome had remained elusive. Here, by focusing on short cis-acting DNA elements of single functions, we discovered, for the first time, to our knowledge, three classes of response elements in human genome: PcG response elements (PREs), MLL1/2-TrxG response elements (TREs) and PcG/TrxG response elements (P/TREs). We further demonstrated that, in contrast to their proposed roles in recruiting PcG proteins to PREs, YY1 and CpG islands are specifically enriched in TREs and P/TREs, but not in PREs. The three classes of response elements as unraveled in this study open new doors for a deeper understanding of PcG and TrxG mechanisms in vertebrates.