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MacroH2A histone variants have functions in differentiation, somatic cell reprogramming and cancer. However, at present, it is not clear how macroH2As affect gene regulation to exert these functions. We have parted from the initial observation that loss of total macroH2A1 led to a change in the morphology of murine myotubes differentiated ex vivo. The fusion of myoblasts to myotubes is a key process in embryonic myogenesis and highly relevant for muscle regeneration after acute or chronic injury. We have focused on this physiological process, to investigate the functions of the two splice isoforms of macroH2A1. Individual perturbation of the two isoforms in myotubes forming in vitro from myogenic C2C12 cells showed an opposing phenotype, with macroH2A1.1 enhancing, and macroH2A1.2 reducing, fusion. Differential regulation of a subset of fusion-related genes encoding components of the extracellular matrix and cell surface receptors for adhesion correlated with these phenotypes. We describe, for the first time, splice isoform-specific phenotypes for the histone variant macroH2A1 in a physiologic process and provide evidence for a novel underlying molecular mechanism of gene regulation.

Polycomb proteins play an essential role in maintaining the repression of developmental genes in self-renewing embryonic stem cells. The exact mechanism allowing the derepression of polycomb target genes during cell differentiation remains unclear. Our project aimed to identify Cbx8 binding sites in differentiating mouse embryonic stem cells. Therefore, we used a genome-wide chromatin immunoprecipitation of endogenous Cbx8 coupled to direct massive parallel sequencing (ChIP-Seq). Our analysis identified 171 high confidence peaks. By crossing our data with previously published microarray analysis, we show that several differentiation genes transiently recruit Cbx8 during their early activation. Depletion of Cbx8 partially impairs the transcriptional activation of these genes. Both interaction analysis, as well as chromatin immunoprecipitation experiments support the idea that activating Cbx8 acts in the context of an intact PRC1 complex. Prolonged gene activation results in eviction of PRC1 despite persisting H3K27me3 and H2A ubiquitination. The composition of PRC1 is highly modular and changes when embryonic stem cells commit to differentiation. We further demonstrate that the exchange of Cbx7 for Cbx8 is required for the effective activation of differentiation genes. Taken together, our results establish a function for a Cbx8-containing complex in facilitating the transition from a Polycomb-repressed chromatin state to an active state. As this affects several key regulatory differentiation genes this mechanism is likely to contribute to the robust execution of differentiation programs.

Background: The empirical evidence accumulated on the efficacy, effectiveness, and efficiency of psychotherapeutic treatments in children and adolescents calls for an update. The main goal of this paper objective was to carry out a selective review of empirically supported psychological treatments for a variety of common psychological disorders and problems in childhood and adolescence. Method: A review was carried out of the psychological treatments for different psychological disorders and problems in socialemotional or behavioral adjustment in the child-adolescent population according to the Spanish National Health System (Clinical Practice Guidelines) levels of evidence and degrees of recommendation. Results: The findings suggest that psychological treatments have empirical support for addressing a wide range of psychological problems in these developmental stages. The degree of empirical support ranges from low to high depending on the phenomenon analyzed. The review suggests unequal progress in the different fields of intervention. Conclusions: From this update, psychologists will be able to make informed decisions when implementing those empirically supported treatments to address the problems that occur in childhood and adolescence. [ABSTRACT FROM AUTHOR]

To analyze how students use online learning tools, such as didactic websites, a common practice is to report global access statistics. Although these are adequate measures, they are not specific enough and do not allow to determine if there are differences depending on the type of resources available to students. The aim of this study is to compare how students use different types of resources in a didactic website, distinguishing between resources to be evaluated in a final exam, resources for work in the classroom, extension resources not to be evaluated, and online extension resources. To this end, the 96 students (87 women, 9 men) taking part in the research enrolled in a subject that is part of the Degree in Speech Therapy, and where a didactic website was used as a tool to complement face-to-face teaching. The total number of accesses to the didactic website and the average number of reads of each type of resources were taken as units of measure. The results indicated that, although the number of visits generally reflected an intense, frequent, stable use of the website, at the same time there were some types of resources that were hardly used by students. Thus, it is suggested that the availability of a particular learning resource on a didactic website does not imply that it will be used, and that the best way to increase the use of a resource is to evaluate it, or to use it in the classroom.