Genome-wide analysis of regions similar to promoters of histone genes

Background: The purpose of this study is to: i) develop a computational model of promoters of human histone-encoding genes (shortly histone genes), an important class of genes that participate in various critical cellular processes, ii) use the model so developed to identify regions across the human genome that have similar structure as promoters of histone genes; such regions could represent potential genomic regulatory regions, e.g. promoters, of genes that may be coregulated with histone genes, and iii/ identify in this way genes that have high likelihood of being coregulated with the histone genes. Results: We successfully developed a histone promoter model using a comprehensive collection of histone genes. Based on leave-one-out cross-validation test, the model produced good prediction accuracy (94.1% sensitivity, 92.6% specificity, and 92.8% positive predictive value). We used this model to predict across the genome a number of genes that shared similar promoter structures with the histone gene promoters. We thus hypothesize that these predicted genes could be coregulated with histone genes. This hypothesis matches well with the available gene expression, gene ontology, and pathways data. Jointly with promoters of the above-mentioned genes, we found a large number of intergenic regions with similar structure as histone promoters. Conclusions: This study represents one of the most comprehensive computational analyses conducted thus far on a genome-wide scale of promoters of human histone genes. Our analysis suggests a number of other human genes that share a high similarity of promoter structure with the histone genes and thus are highly likely to be coregulated, and consequently coexpressed, with the histone genes. We also found that there are a large number of intergenic regions across the genome with their structures similar to promoters of histone genes. These regions may be promoters of yet unidentified genes, or may represent remote control regions that participate in regulation of histone and histone-coregulated gene transcription initiation. While these hypotheses still remain to be verified, we believe that these form a useful resource for researchers to further explore regulation of human histone genes and human genome. It is worthwhile to note that the regulatory regions of the human genome remain largely un-annotated even today and this study is an attempt to supplement our understanding of histone regulatory regions.Statistic

Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing

Cell cycle and replication need to be tightly regulated to ensure genome stability in mammalian cells. Here the authors provide a link between chromatin structure and DNA replication regulation by showing that chromatin compaction limits replication licensing thereby promoting genome integrity

Histone H1 Subtypes Differentially Modulate Chromatin Condensation without Preventing ATP-Dependent Remodeling by SWI/SNF or NURF

Although ubiquitously present in chromatin, the function of the linker histone subtypes is partly unknown and contradictory studies on their properties have been published. To explore whether the various H1 subtypes have a differential role in the organization and dynamics of chromatin we have incorporated all of the somatic human H1 subtypes into minichromosomes and compared their influence on nucleosome spacing, chromatin compaction and ATP-dependent remodeling. H1 subtypes exhibit different affinities for chromatin and different abilities to promote chromatin condensation, as studied with the Atomic Force Microscope. According to this criterion, H1 subtypes can be classified as weak condensers (H1.1 and H1.2), intermediate condensers (H1.3) and strong condensers (H1.0, H1.4, H1.5 and H1x). The variable C-terminal domain is required for nucleosome spacing by H1.4 and is likely responsible for the chromatin condensation properties of the various subtypes, as shown using chimeras between H1.4 and H1.2. In contrast to previous reports with isolated nucleosomes or linear nucleosomal arrays, linker histones at a ratio of one per nucleosome do not preclude remodeling of minichromosomes by yeast SWI/SNF or Drosophila NURF. We hypothesize that the linker histone subtypes are differential organizers of chromatin, rather than general repressors

Neoconservatism as Discourse:Virtue, Power and US Foreign Policy

Neoconservatism in US foreign policy is a hotly contested subject, yet most scholars broadly agree on what it is and where it comes from. From a consensus that it first emerged around the 1960s, these scholars view neoconservatism through what we call the ‘3Ps’ approach, defining it as a particular group of people (‘neocons’), an array of foreign policy preferences and/or an ideological commitment to a set of principles. While descriptively intuitive, this approach reifies neoconservatism in terms of its specific and often static ‘symptoms’ rather than its dynamic constitutions. These reifications may reveal what is emblematic of neoconservatism in its particular historical and political context, but they fail to offer deeper insights into what is constitutive of neoconservatism. Addressing this neglected question, this article dislodges neoconservatism from itsperceived home in the ‘3Ps’ and ontologically redefines it as a discourse. Adopting aFoucauldian approach of archaeological and genealogical discourse analysis, we trace itsdiscursive formations primarily to two powerful and historically enduring discourses ofthe American self — virtue and power — and illustrate how these discourses produce aparticular type of discursive fusion that is ‘neoconservatism’. We argue that to betterappreciate its continued effect on contemporary and future US foreign policy, we needto pay close attention to those seemingly innocuous yet deeply embedded discoursesabout the US and its place in the world, as well as to the people, policies and principlesconventionally associated with neoconservatism