Group: Genetics-of-Gambling - with tag transcriptional-regulation [20 articles]

Abstract

The identification and characterization of mammalian core promoters and transcription start sites is a prerequisite to understanding how RNA polymerase II transcription is controlled. New experimental technologies have enabled genome-wide discovery and characterization of core promoters, revealing that most mammalian genes do not conform to the simple model in which a TATA box directs transcription from a single defined nucleotide position. In fact, most genes have multiple promoters, within which there are multiple start sites, and alternative promoter usage generates diversity ...

Abstract

Recent evidence of genome-wide transcription in several species indicates that the amount of transcription that occurs cannot be entirely accounted for by current sets of genome-wide annotations. Evidence indicates that most of both strands of the human genome might be transcribed, implying extensive overlap of transcriptional units and regulatory elements. These observations suggest that genomic architecture is not colinear, but is instead interleaved and modular, and that the same genomic sequences are multifunctional: that is, used for multiple independently regulated transcripts ...

Abstract

Transcription factor complexes bind to regulatory sequences of genes, providing a system of individual expression regulation. Targets of distinct transcription factors usually map throughout the genome, without clustering. Nevertheless, highly and weakly expressed genes do cluster in separate chromosomal domains with an average size of 8090 genes. We therefore asked whether, besides transcription factors, an additional level of gene expression regulation exists that acts on chromosomal domains. Here we show that identical green fluorescent protein (GFP) reporter constructs integrated at 90 ...

Abstract

We imaged transcription in living cells using a locus-specific reporter system, which allowed precise, single-cell kinetic measurements of promoter binding, initiation and elongation. Photobleaching of fluorescent RNA polymerase II revealed several kinetically distinct populations of the enzyme interacting with a specific gene. Photobleaching and photoactivation of fluorescent MS2 proteins used to label nascent messenger RNAs provided sensitive elongation measurements. A mechanistic kinetic model that fits our data was validated using specific inhibitors. Polymerases elongated at 4.3 kilobases min(-1), much faster than ...

Abstract

We demonstrate that the binding sites for highly conserved transcription factors vary extensively between human and mouse. We mapped the binding of four tissue-specific transcription factors (FOXA2, HNF1A, HNF4A and HNF6) to 4,000 orthologous gene pairs in hepatocytes purified from human and mouse livers. Despite the conserved function of these factors, from 41% to 89% of their binding events seem to be species specific. When the same protein binds the promoters of orthologous genes, approximately two-thirds of the binding sites do ...

Abstract

In studies of their transcriptional activity, genomes have shown a high order of organization. We assessed the question of how genomically neighboring genes are transcriptionally coupled across tissues and what could be the driving force behind their coupling. We focused our analysis on the transcriptome information for 13 tissues of Mus musculus and 79 tissues of Homo sapiens. The analysis of coexpression patterns of genomically adjacent genes across tissues revealed 2619 and 1275 clusters of highly coexpressed genes, respectively. Most of ...

Abstract

Individual cells in genetically homogeneous populations have been found to express different numbers of molecules of specific proteins. We investigated the origins of these variations in mammalian cells by counting individual molecules of mRNA produced from a reporter gene that was stably integrated into the cell's genome. We found that there are massive variations in the number of mRNA molecules present in each cell. These variations occur because mRNAs are synthesized in short but intense bursts of transcription beginning when the ...

Abstract

The regulation of gene expression is mediated by interactions between chromatin and protein complexes. The importance of where and when these interactions take place in the nucleus is currently a subject of intense investigation. Increasing evidence indicates that gene activation or silencing is often associated with repositioning of the locus relative to nuclear compartments and other genomic loci. At the same time, however, structural constraints impose limits on chromatin mobility. Understanding how the dynamic nature of the positioning of genetic material ...

Abstract

Comparative genomic studies have been useful in identifying transcriptional regulatory elements in higher eukaryotic genomes, but many important regulatory elements cannot be detected by such analyses due to evolutionary variations and alignment tool limitations. Therefore, in this study we exploit the highly conserved nature of epigenetic modifications to identify potential transcriptional enhancers. By using a high-resolution genome-wide mapping technique, which combines the chromatin immunoprecipitation and serial analysis of gene expression assays, we have recently determined the distribution of lysine 9/14-diacetylated histone ...

Abstract

The relationships among in vivo chromatin structures, chromosome organization and genome function must be understood in order to reveal the hidden regulatory information in our genomes. Rather than being stable architectural features, it appears that chromatin and chromosome conformations at all levels are highly dynamic, which is the key to their function. Studies in recent years have elucidated long-range interactions or folded chromatin conformations that play significant roles in gene regulation. Most recently, intrachromosomal associations and co-associations with shared nuclear transcription ...

Abstract

Eukaryotic gene expression can be viewed within a conceptual framework in which regulatory mechanisms are integrated at three hierarchical levels. The first is the sequence level, i.e. the linear organization of transcription units and regulatory sequences. Here, developmentally co-regulated genes seem to be organized in clusters in the genome, which constitute individual functional units. The second is the chromatin level, which allows switching between different functional states. Switching between a state that suppresses transcription and one that is permissive for gene ...

Abstract

Control of eukaryotic gene expression involves combinatorial interactions between transcription factors and regulatory sequences in the genome. In addition, chromatin structure and modification states play key roles in determining the competence of transcription. The term 'transcriptional regulatory code' has been used to describe the interplay of these events in the complex control of transcription. With the maturation of methods for detecting in vivo protein-DNA interactions on a genome-wide scale, detailed maps of chromatin features and transcription factor localization over entire genomes ...

Abstract

Transcription factors in the germline play important roles in ovary formation and folliculogenesis, and control both oocyte development and somatic cell function. Factor in the germline (Figla) and newborn ovary homeobox gene (Nobox) represent a growing number of oocyte-specific transcription factors that regulate genes unique to oocytes. Studies on oocyte-specific transcription factors are important in understanding the genetic pathways essential for oogenesis, pluripotency, and embryonic development. Likely, these genes regulate reproductive life span and represent candidate genes for reproductive disorders, such ...