In eukaryotes, DNA is packed inside the cell nucleus in the form of chromatin, which consists of DNA, proteins such as histones, and RNA. Euchromatin, which is permissive for transcription, is spatially organized into transcriptionally inactive domains interspersed with pockets of transcriptional activity. While transcription and RNA have been implicated in euchromatin organization, it remains unclear how their interplay forms and maintains transcription pockets. Here we combine theory and experiment to analyze the dynamics of euchromatin organization as pluripotent zebrafish cells exit mitosis and begin transcription. We show that accumulation of RNA induces formation of transcription pockets which displace transcriptionally inactive chromatin. We propose that the accumulating RNA recruits RNA-binding proteins that together tend to separate from transcriptionally inactive euchromatin. Full phase separation is prevented because RNA remains tethered to transcribed euchromatin through RNA polymerases. Instead, smaller scale microphases emerge that do not grow further and form the typical pattern of euchromatin organization.

Cognitive decline, especially the slowing of information processing speed, is associated with normal ageing. This decline may be due to brain cortico-cortical disconnection caused by age-related white matter deterioration. We present results from a large, narrow age range cohort of generally healthy, community-dwelling subjects in their seventies who also had their cognitive ability tested in youth (age 11 years). We investigate associations between older age brain white matter structure, several measures of information processing speed and childhood cognitive ability in 581 subjects. Analysis of diffusion tensor MRI data using Tract-based Spatial Statistics (TBSS) showed that all measures of information processing speed, as well as a general speed factor composed from these tests (gspeed), were significantly associated with fractional anisotropy (FA) across the white matter skeleton rather than in specific tracts. Cognitive ability measured at age 11 years was not associated with older age white matter FA, except for the gspeed-independent components of several individual processing speed tests. These results indicate that quicker and more efficient information processing requires global connectivity in older age, and that associations between white matter FA and information processing speed (both individual test scores and gspeed), unlike some other aspects of later life brain structure, are generally not accounted for by cognitive ability measured in youth.

The National Institute of Mental Health's Research Domain Criteria (RDoC) Initiative “calls for the development of new ways of classifying psychopathology based on dimensions of observable behavior.” As a result of this ambitious initiative, language has been identified as an independent construct in the RDoC matrix. In this article, we frame language within an evolutionary and neuropsychological context and discuss some of the limitations to the current measurements of language. Findings from genomics and the neuroimaging of performance during language tasks are discussed in relation to serious mental illness and within the context of caveats regarding measuring language. Indeed, the data collection and analysis methods employed to assay language have been both aided and constrained by the available technologies, methodologies, and conceptual definitions. Consequently, different fields of language research show inconsistent definitions of language that have become increasingly broad over time. Individually, they have also shown significant improvements in conceptual resolution, as well as in experimental and analytic techniques. More recently, language research has embraced collaborations across disciplines, notably neuroscience, cognitive science, and computational linguistics and has ultimately re‐defined classical ideas of language. As we move forward, the new models of language with their remarkably multifaceted constructs force a re‐examination of the NIMH RDoC conceptualization of language and thus the neuroscience and genetics underlying this concept. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

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The localization of transcriptional activity in specialized transcription bodies is a hallmark of gene expression in eukaryotic cells. How proteins of the transcriptional machinery come together to form such bodies, however, is unclear. Here, we take advantage of two large, isolated, and long-lived transcription bodies that reproducibly form during early zebrafish embryogenesis, to characterize the dynamics of transcription body formation. Once formed, these transcription bodies are enriched for initiating and elongating RNA polymerase II, as well as the transcription factors Nanog and Sox19b. Analyzing the events leading up to transcription, we find that Nanog and Sox19b cluster prior to transcription, and independently of RNA accumulation. The clustering of transcription factors is sequential; Nanog clusters first, and this is required for the clustering of Sox19b and the initiation of transcription. Mutant analysis revealed that both the DNA-binding domain, as well as one of the two intrinsically disordered regions of Nanog are required to organize the two bodies of transcriptional activity. Taken together, our data suggests that the clustering of transcription factors dictates the formation of transcription bodies.

Somatic embryogenesis (SE) is the development of embryo-like structures from somatic plant tissues. This process rarely can be observed in nature, but for many plant species, in vitro protocols are developed, which allow to obtain somatic embryos formation directly from tissues of plant explant or from the embryogenic callus. SE is widely used for plant propagation and transformation; therefore, the search for SE stimulators and revealing of the mechanisms of their functioning are very important for biotechnology. Among the SE regulators, proteins of the WOX family play significant roles. WOX (WUSCHEL-RELATED HOMEOBOX) is a homeodomain-containing transcription factor family. Different WOX genes function in different plant organs and tissues, maintaining meristem activity and regulating cell proliferation and differentiation. Recently, we have shown that transcription factor MtWOX9-1, belonging to the WOX family, can stimulate SE in the Medicago truncatula callus culture. In this research, transcriptomic analysis of highly embryogenic calli with MtWOX9-1 overexpression was performed in comparison to wildtype calli. It was shown that MtWOX9-1 overexpression led to the activation of several groups of genes, including genes related to cell division, tissue diff erentiation, and seed development. Enriched GO pathways included several groups related to histone methyltransferase activity as well as DNA methylation and chromatin binding, suggesting major epigenetic changes that occur in call overexpressing MtWOX9-1. Using Medicago Truncatula Gene Expression Atlas, we also iden tified a group of genes coding for transcription factors that were both coexpressed with MtWOX9-1 in different plant organs and differentially expressed in our samples. These genes are putative targets of MtWOX9-1, and they may act in the same pathway with this regulator during SE.

The localization of transcriptional activity in specialized transcription bodies is a hallmark of gene expression in eukaryotic cells, but it remains unclear if and how they affect gene expression. Here, we disrupted the formation of two prominent transcription bodies that mark the onset of zygotic transcription in zebrafish embryos and analyzed the effect on gene expression using enriched SLAM-Seq and live-cell imaging. We found that the disruption of transcription bodies results in the upregulation of genes that already have accessible chromatin and are poised to be transcribed when the two transcription bodies are present. Live-cell imaging suggests that the disruption of these transcription bodies enables poised genes to be transcribed in ectopic transcription bodies. Our results suggest that transcription bodies regulate transcription genome-wide by sequestering components of the transcriptional machinery.

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