The lateral septum (LS), a GABAergic structure located in the basal forebrain, is implicated in social behavior, learning and memory. We previously demonstrated that expression of tropomyosin kinase receptor B (TrkB) in LS neurons is required for social novelty recognition. To better understand molecular mechanisms by which TrkB signaling controls behavior, we locally knocked down TrkB in LS and used bulk RNA-sequencing to identify changes in gene expression downstream of TrkB. TrkB knockdown induces upregulation of genes associated with inflammation and immune responses, and downregulation of genes associated with synaptic signaling and plasticity. Next, we generated one of the first atlases of molecular profiles for LS cell types using single nucleus RNA-sequencing (snRNA-seq). We identified markers for the septum broadly, and the LS specifically, as well as for all neuronal cell types. We then investigated whether the differentially expressed genes (DEGs) induced by TrkB knockdown map to specific LS cell types. Enrichment testing identified that downregulated DEGs are broadly expressed across neuronal clusters. Enrichment analyses of these DEGs demonstrated that downregulated genes are uniquely expressed in the LS, and associated with either synaptic plasticity or neurodevelopmental disorders. Upregulated genes are enriched in LS microglia, associated with immune response and inflammation, and linked to both neurodegenerative disease and neuropsychiatric disorders. In addition, many of these genes are implicated in regulating social behaviors. In summary, the findings implicate TrkB signaling in the LS as a critical regulator of gene networks associated with psychiatric disorders that display social deficits, including schizophrenia and autism, and with neurodegenerative diseases, including Alzheimer's.

Ewing sarcoma (ES) is a primary bone marrow tumor that very rarely develops in extra-osseous tissues, such as lung. The hallmark of ES tumors is a translocation between chromosomes 11 and 22, resulting in a fusion protein, commonly referred to as EWS-FLI1. The epigenetic profile (histone acetylation and methylation enrichment of the promoter region) that may regulate the expression of the aberrant transcription factor EWS-FLI1, remains poorly studied and understood. Knowledge of epigenetic patterns associated with covalent histone modification and expression of enzymes associated with this process, can contribute to the understanding of the molecular basis of the disease, as well as to the identification of possible molecular targets involved in expression of the EWS-FLI1 gene, so that therapeutic strategies may be improved in the future. In the present study, the transcriptional activation and repression of the EWS-FLI1 fusion gene in ES was accompanied by selective deposition of histone markers on its promoter. The EWS-FLI1 fusion gene was evaluated in two patients with ES using conventional cytogenetic, fluorescence in situ hybridization and nested PCR assays, which revealed that the aberrant expression of the EWS-FLI1 gene is accompanied by enrichment of H3K4Me3, H3K9ac and H3K27ac at the promoter region.

El proceso transición epitelio mesénquima (TEM) permite que una célula epitelial de manera temporal, adquiera un fenotipo mesenquimal como respuesta a un estímulo interno o externo. Este proceso se caracteriza  por la activación y represión de genes involucrados en diferentes vías de señalización asociadas con migración, invasión y apoptosis, entre otros. En este proceso la epigenética cumple un papel fundamental. La epigenética comprende cuatro mecanismos: metilación de ADN, modificación covalente de histonas, ARN no codificantes (ARNnc) y complejos remodeladores de la cromatina, que regulan la expresión de un gen sin alterar su secuencia. En esta revisión de tema los autores describen los principales mecanismos epigenéticos involucrados en la regulación de la expresión de genes que se activan y reprimen concomitantemente en las tres fases del proceso TEM: fase no migratoria, fase premigratoria y fase migratoria.