RESUMO
Autism Spectrum Disorder (ASD) is the most prevalent neurodevelopmental disorder in the United States and often co-presents with sleep problems. Sleep problems in ASD predict the severity of ASD core diagnostic symptoms and have a considerable impact on the quality of life of caregivers. Little is known, however, about the underlying molecular mechanisms of sleep problems in ASD. We investigated the role of Shank3, a high confidence ASD gene candidate, in sleep architecture and regulation. We show that mice lacking exon 21 of Shank3 have problems falling asleep even when sleepy. Using RNA-seq we show that sleep deprivation increases the differences in prefrontal cortex gene expression between mutants and wild types, downregulating circadian transcription factors Per3, Bhlhe41, Hlf, Tef, and Nr1d1. Shank3 mutants also have trouble regulating wheel-running activity in constant darkness. Overall, our study shows that Shank3 is an important modulator of sleep and clock gene expression.
Assuntos
Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/biossíntese , Regulação da Expressão Gênica , Proteínas do Tecido Nervoso/metabolismo , Sono , Fatores de Transcrição/metabolismo , Animais , Perfilação da Expressão Gênica , Camundongos , Proteínas dos Microfilamentos , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Proteínas do Tecido Nervoso/genética , Análise de Sequência de RNARESUMO
It has been long thought that RNA Polymerase (Pol) II transcriptional regulation does not operate in trypanosomes. However, recent reports have suggested that these organisms could regulate RNA Pol II transcription by epigenetic mechanisms. In this paper, we investigated the role of TbRRM1 in transcriptional regulation of RNA Pol II-dependent genes by focusing both in genes located in a particular polycistronic transcription unit (PTU) and in the monocistronic units of the SL-RNA genes. We showed that TbRRM1 is recruited throughout the PTU, with a higher presence on genes than intergenic regions. However, its depletion leads both to the decrease of nascent RNA and to chromatin compaction only of regions located distal to the main transcription start site. These findings suggest that TbRRM1 facilitates the RNA Pol II transcriptional elongation step by collaborating to maintain an open chromatin state in particular regions of the genome. Interestingly, the SL-RNA genes do not recruit TbRRM1 and, after TbRRM1 knockdown, nascent SL-RNAs accumulate while the chromatin state of these regions remains unchanged. Although it was previously suggested that TbRRM1 could regulate RNA Pol II-driven genes, we provide here the first experimental evidence which involves TbRRM1 to transcriptional regulation.
Assuntos
Proteínas de Protozoários/genética , RNA Polimerase II/genética , Proteínas de Ligação a RNA/metabolismo , Trypanosoma brucei brucei/metabolismo , Regulação da Expressão Gênica , Proteínas de Protozoários/metabolismo , RNA Polimerase II/metabolismo , Proteínas de Ligação a RNA/genética , Transcrição Gênica , Trypanosoma brucei brucei/genéticaRESUMO
The integration of ecology and genetics has become established in recent decades, in hand with the development of new technologies, whose implementation is allowing an improvement of the tools used for data analysis. In a landscape genetics context, integrative management of population information from different sources can make spatial studies involving phenotypic, genotypic and environmental data simpler, more accessible and faster. Tools for exploratory analysis of autocorrelation can help to uncover the spatial genetic structure of populations and generate appropriate hypotheses in searching for possible causes and consequences of their spatial processes. This study presents EcoGenetics, an R package with tools for multisource management and exploratory analysis in landscape genetics.
Assuntos
Biodiversidade , Bioestatística/métodos , Genética Populacional/métodos , Análise EspacialRESUMO
PREMISE OF THE STUDY: Gene flow through dispersal of seeds and pollen is a fundamental determinant of spatial genetic structure (SGS) in natural populations of trees at different spatial scales. Within continuous populations, restrictions to gene flow should be manifested in a process of local genetic differentiation, known as isolation by distance. The present work examines the SGS of a Prosopis alba population in a patchy region where urban, forest, and agricultural areas coexist. The analysis discussed here expands our knowledge about the processes affecting the distribution of the genetic variability in populations of disturbed landscapes. METHODS: Three sites with different landscape and demographic characteristics were analyzed. Seven highly variable microsatellite markers were used to survey the relevance of both isolation by distance and stochastic migration in the SGS of the population. KEY RESULTS: The analyses showed that (1) the genetic similarity declined with increasing geographic distance, (2) the population may be conceived as a single genetically continuous unit showing spatial differentiation as consequence of isolation by distance, rather than a structured population following the island model, and (3) there is evidence supporting a past immigration event into one of the study sites, which promoted a local pattern of genetic structure. CONCLUSIONS: These results indicate that in spite of the population fragmentation produced by land-use changes, P. alba maintains the genetic cohesion and a continuous genetic structure in the analyzed area.