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1.
EMBO J ; 36(19): 2887-2906, 2017 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-28871058

RESUMEN

In metazoans, the pausing of RNA polymerase II at the promoter (paused Pol II) has emerged as a widespread and conserved mechanism in the regulation of gene transcription. While critical in recruiting Pol II to the promoter, the role transcription factors play in transitioning paused Pol II into productive Pol II is, however, little known. By studying how Drosophila Hox transcription factors control transcription, we uncovered a molecular mechanism that increases productive transcription. We found that the Hox proteins AbdA and Ubx target gene promoters previously bound by the transcription pausing factor M1BP, containing paused Pol II and enriched with promoter-proximal Polycomb Group (PcG) proteins, yet lacking the classical H3K27me3 PcG signature. We found that AbdA binding to M1BP-regulated genes results in reduction in PcG binding, the release of paused Pol II, increases in promoter H3K4me3 histone marks and increased gene transcription. Linking transcription factors, PcG proteins and paused Pol II states, these data identify a two-step mechanism of Hox-driven transcription, with M1BP binding leading to Pol II recruitment followed by AbdA targeting, which results in a change in the chromatin landscape and enhanced transcription.


Asunto(s)
Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/fisiología , Regulación de la Expresión Génica , Proteínas de Homeodominio/fisiología , Proteínas Nucleares/fisiología , Factores de Transcripción/metabolismo , Factores de Transcripción/fisiología , Transcripción Genética/genética , Animales , Animales Modificados Genéticamente , Células Cultivadas , Proteínas de Drosophila/genética , Drosophila melanogaster/embriología , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Embrión no Mamífero , Femenino , Proteínas de Homeodominio/metabolismo , Masculino , Proteínas Nucleares/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , ARN Polimerasa II/metabolismo
2.
BMC Genomics ; 20(1): 250, 2019 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-30922228

RESUMEN

BACKGROUND: The last 10 years have seen the rise of countless functional genomics studies based on Next-Generation Sequencing (NGS). In the vast majority of cases, whatever the species, whatever the experiment, the two first steps of data analysis consist of a quality control of the raw reads followed by a mapping of those reads to a reference genome/transcriptome. Subsequent steps then depend on the type of study that is being made. While some tools have been proposed for investigating data quality after the mapping step, there is no commonly adopted framework that would be easy to use and broadly applicable to any NGS data type. RESULTS: We present ALFA, a simple but universal tool that can be used after the mapping step on any kind of NGS experiment data for any organism with available genomic annotations. In a single command line, ALFA can compute and display distribution of reads by categories (exon, intron, UTR, etc.) and biotypes (protein coding, miRNA, etc.) for a given aligned dataset with nucleotide precision. We present applications of ALFA to Ribo-Seq and RNA-Seq on Homo sapiens, CLIP-Seq on Mus musculus, RNA-Seq on Saccharomyces cerevisiae, Bisulfite sequencing on Arabidopsis thaliana and ChIP-Seq on Caenorhabditis elegans. CONCLUSIONS: We show that ALFA provides a powerful and broadly applicable approach for post mapping quality control and to produce a global overview using common or dedicated annotations. It is made available to the community as an easy to install command line tool and from the Galaxy Tool Shed.


Asunto(s)
Arabidopsis/genética , Caenorhabditis elegans/genética , Biología Computacional/métodos , Saccharomyces cerevisiae/genética , Animales , Perfilación de la Expresión Génica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Ratones , Anotación de Secuencia Molecular , Análisis de Secuencia de ARN , Programas Informáticos
3.
Genome Biol Evol ; 9(1): 1-6, 2017 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-28173009

RESUMEN

Oryza glaberrima is one of the two cultivated species of rice, and harbors various interesting agronomic traits, especially in biotic and abiotic resistance, compared with its Asian cousin O. sativa. A previous reference genome was published but newer studies highlighted some missing parts. Moreover, global species diversity is known nowadays to be represented by more than one single individual. For that purpose, we sequenced, assembled and annotated de novo three different cultivars from O. glaberrima. After validating our assemblies, we were able to better solve complex regions than the previous assembly and to provide a first insight in pan-genomic divergence between individuals. The three assemblies shown large common regions, but almost 25% of the genome present collinearity breakpoints or are even individual specific.


Asunto(s)
Genoma de Planta , Oryza/clasificación , Oryza/genética , África , Variación Genética , Anotación de Secuencia Molecular , Análisis de Secuencia de ADN
4.
Cell Discov ; 3: 17005, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28377822

RESUMEN

Astrocytes send out long processes that are terminated by endfeet at the vascular surface and regulate vascular functions as well as homeostasis at the vascular interface. To date, the astroglial mechanisms underlying these functions have been poorly addressed. Here we demonstrate that a subset of messenger RNAs is distributed in astrocyte endfeet. We identified, among this transcriptome, a pool of messenger RNAs bound to ribosomes, the endfeetome, that primarily encodes for secreted and membrane proteins. We detected nascent protein synthesis in astrocyte endfeet. Finally, we determined the presence of smooth and rough endoplasmic reticulum and the Golgi apparatus in astrocyte perivascular processes and endfeet, suggesting for local maturation of membrane and secreted proteins. These results demonstrate for the first time that protein synthesis occurs in astrocyte perivascular distal processes that may sustain their structural and functional polarization at the vascular interface.

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