The information contained within the linear sequence of bases (the genome) must be faithfully replicated in each cell cycle, with a balance of constancy and variation taking place over the course of evolution. Recently, it has become clear that additional information important for genetic regulation is contained within the chromatin proteins associated with DNA (the epigenome). Epigenetic information also must be faithfully duplicated in each cell cycle, with a balance of constancy and variation taking place during the course of development (...) to achieve differentiation while maintaining identity within cell lineages. Both the genome and the epigenome are synthesized at the replication fork, so the events occurring during S‐phase provide a critical window of opportunity for eliciting change or maintaining existing genetic states. Cells discriminate between different states of chromatin through the activities of proteins that selectively modify the structure of chromatin. Several recent studies report the localization of certain chromatin modifying proteins to replication forks at specific times during S‐phase. Since transcriptionally active and inactive chromosome domains generally replicate at different times during S‐phase, this spatiotemporal regulation of chromatin assembly proteins may be an integral part of epigenetic inheritance. BioEssays 25:647–656, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The central dogma of biology holds that genetic information normally flows from DNA to RNA to protein. As a consequence it has been generally assumed that genes generally code for proteins, and that proteins fulfil not only most structural and catalytic but also most regulatory functions, in all cells, from microbes to mammals. However, the latter may not be the case in complex organisms. A number of startling observations about the extent of non-protein-coding RNA (ncRNA) transcription in the higher eukaryotes (...) and the range of genetic and epigenetic phenomena that are RNA-directed suggests that the traditional view of the structure of genetic regulatory systems in animals and plants may be incorrect. ncRNA dominates the genomic output of the higher organisms and has been shown to control chromosome architecture, mRNA turnover and the developmental timing of protein expression, and may also regulate transcription and alternative splicing. This paper re-examines the available evidence and suggests a new framework for considering and understanding the genomic programming of biological complexity, autopoletic development and phenotypic variation. BioEssays 25:930-939,2003. (C) 2003 Wiley Periodicals, Inc. (shrink)

Local differences in chromatin organisation may profoundly affect the activity of eukaryotic genomes. Regulation at the level of DNA packaging requires the targeting of structural proteins and histone‐modifying enzymes to specific sites and their stable or dynamic interaction with the nucleosomal fiber. The “chromodomain”, a domain shared by many regulators of chromatin structure, has long been suspected to serve as a module mediating chromatin interactions in a variety of different protein contexts. However, recent functional analyses of a number of different (...) chromodomains revealed an unexpected diversity of interaction targets, including histones, DNA and even RNA. The chromodomains of today seem to have evolved from a common ancestral fold to fulfill various functions in different molecular contexts. Combining information gained from recent functional and structural studies of chromodomains with a bioinformatic classification of their structure could lead to the definition of sequence motifs with predictive quality for chromodomain function. BioEssays 26:133–140, 2004. © 2004 Wiley Periodicals, Inc. (shrink)