CpG-Methylation Regulates a Class of Epstein-Barr Virus Promoters

DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian gene regulation. In general, cytosine-phosphatidyl-guanosine (CpG)-methylated promoters are transcriptionally repressed and nuclear proteins such as MECP2, MBD1, MBD2, and MBD4 bind CpG-methylated DNA and contribute to epigenetic silencing. Methylation of viral DNA also regulates gene expression of Epstein-Barr virus (EBV), which is a model of herpes virus latency. In latently infected human B cells, the viral DNA is CpG-methylated, the majority of viral genes is repressed and virus synthesis is therefore abrogated. EBV's BZLF1 encodes a transcription factor of the AP-1 family (Zta) and is the master gene to overcome viral gene repression. In a genome-wide screen, we now identify and characterize those viral genes, which Zta regulates. Among them are genes essential for EBV's lytic phase, which paradoxically depend on strictly CpG-methylated promoters for their Zta-induced expression. We identified novel DNA recognition motifs, termed meZRE (methyl-Zta-responsive element), which Zta selectively binds in order to ‘read’ DNA in a methylation- and sequence-dependent manner unlike any other known protein. Zta is a homodimer but its binding characteristics to meZREs suggest a sequential, non-palindromic and bipartite DNA recognition element, which confers superior DNA binding compared to CpG-free ZREs. Our findings indicate that Zta has evolved to transactivate cytosine-methylated, hence repressed, silent promoters as a rule to overcome epigenetic silencing

The Princeton Protein Orthology Database (P-POD): A Comparative Genomics Analysis Tool for Biologists

Many biological databases that provide comparative genomics information and tools are now available on the internet. While certainly quite useful, to our knowledge none of the existing databases combine results from multiple comparative genomics methods with manually curated information from the literature. Here we describe the Princeton Protein Orthology Database (P-POD, http://ortholog.princeton.edu), a user-friendly database system that allows users to find and visualize the phylogenetic relationships among predicted orthologs (based on the OrthoMCL method) to a query gene from any of eight eukaryotic organisms, and to see the orthologs in a wider evolutionary context (based on the Jaccard clustering method). In addition to the phylogenetic information, the database contains experimental results manually collected from the literature that can be compared to the computational analyses, as well as links to relevant human disease and gene information via the OMIM, model organism, and sequence databases. Our aim is for the P-POD resource to be extremely useful to typical experimental biologists wanting to learn more about the evolutionary context of their favorite genes. P-POD is based on the commonly used Generic Model Organism Database (GMOD) schema and can be downloaded in its entirety for installation on one's own system. Thus, bioinformaticians and software developers may also find P-POD useful because they can use the P-POD database infrastructure when developing their own comparative genomics resources and database tools

(In)Consistency Between Private and Public Disclosure on Enterprise Risk Management and Its Determinants

Worldwidegovernanceorganizationsandregulatorshaverecentlycalled for more enhanced disclosures about how organizations manage risks. Enter- prise Risk Management (ERM) is recognized as a value-contributing best prac- tice even when legal standards do not require it (Whitman in Risk Manag Insur Rev 18(2):161–197, 2015), but public disclosure on such a process is not generally mandatory. In Italy emphasis on risk disclosure started in 2008 but it was the 2011 revision of the Corporate Governance (CG) code for listed companies to ask for the board commitment in disclosing, within the CG report, about the main internal control and risk management system’s characteristics (Borsa Italiana in Codice di Autodisciplina, 2011). Given the proprietary nature of risk information in addition to the Italian capital market characteristics (small capitalization and presence of a domi- nant shareholder) and the lack of any mandate for what specific aspects board should disclose, the study aims at investigating a potential variation between private and public disclosure on ERM. Relying on the ERM concepts provided by the COSO framework (2004) the author submitted a survey seeking information about ERM practices within Italian listed companies. Such a private information is compared to public CG reports released by the same companies. The comparison shows compa- nies tend to privately reveal a more effective ERM process than the one they publicly disclose. An examination of CG and firm’s risk variables potentially determining higher variation—i.e. information inconsistency—supports proprietary costs theory rather than agency theory expectations. Thus showing the limits of voluntary dis- closure dealing with risk management systems. The study might have international policy implications