Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide has ...successfully identified specific subtypes of regulatory elements. In Drosophila several pioneering studies have provided genome-wide identification of Polycomb response elements, chromatin states, transcription factor binding sites, RNA polymerase II regulation and insulator elements; however, comprehensive annotation of the regulatory genome remains a significant challenge. Here we describe results from the modENCODE cis-regulatory annotation project. We produced a map of the Drosophila melanogaster regulatory genome on the basis of more than 300 chromatin immunoprecipitation data sets for eight chromatin features, five histone deacetylases and thirty-eight site-specific transcription factors at different stages of development. Using these data we inferred more than 20,000 candidate regulatory elements and validated a subset of predictions for promoters, enhancers and insulators in vivo. We identified also nearly 2,000 genomic regions of dense transcription factor binding associated with chromatin activity and accessibility. We discovered hundreds of new transcription factor co-binding relationships and defined a transcription factor network with over 800 potential regulatory relationships.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
During each operation of the ventilation system, noise is generated, which is related to the operation of the fan during the transport of air. Attention must be paid to this noise, as the noise and ...depressions caused by the fan are transmitted through the pipes to the air distribution elements and thus disturb the indoor environment of the buildings. Each part of the ventilation system either absorbs or generates noise. Noise propagating and generated in pipes and fittings can be reduced in several ways, for example by dimensioning the pipes. However, noise and vibration that occur directly in the air handling unit must be eliminated in another way. Therefore, a component called a silencer is installed directly behind the air handling unit. For the correct operation of the dampers, it is necessary to monitor not only their acoustic attenuation, but also its pressure loss. The aim of this work is to verify the authenticity of the values given by the calculation program from the company Technov. To achieve the goal, it was necessary to build a measurement-verified CFD model, which would allow the calculation for silencers with other dimensions.
Abstract
Gene regulatory elements, including promoters, enhancers, silencers, etc., control transcriptional programs in a spatiotemporal manner. Though these elements are known to be able to induce ...either positive or negative transcriptional control, the community has been mostly studying enhancers which amplify transcription initiation, with less emphasis given to silencers which repress gene expression. To facilitate the study of silencers and the investigation of their potential roles in transcriptional control, we developed SilencerDB (http://health.tsinghua.edu.cn/silencerdb/), a comprehensive database of silencers by manually curating silencers from 2300 published articles. The current version, SilencerDB 1.0, contains (1) 33 060 validated silencers from experimental methods, and (ii) 5 045 547 predicted silencers from state-of-the-art machine learning methods. The functionality of SilencerDB includes (a) standardized categorization of silencers in a tree-structured class hierarchy based on species, organ, tissue and cell line and (b) comprehensive annotations of silencers with the nearest gene and potential regulatory genes. SilencerDB, to the best of our knowledge, is the first comprehensive database at this scale dedicated to silencers, with reliable annotations and user-friendly interactive database features. We believe this database has the potential to enable advanced understanding of silencers in regulatory mechanisms and to empower researchers to devise diverse applications of silencers in disease development.
Histone modification H3K27me3 is an important chromatin mark that plays vital roles in repressing expression of developmental genes. Here, we construct high-resolution 3D genome maps using long-read ...chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) and characterize H3K27me3-associated chromatin interactions in an elite rice hybrid, Shanyou 63. We find that many H3K27me3-marked regions may function as silencer-like regulatory elements. The silencer-like elements can come into proximity with distal target genes via forming chromatin loops in 3D space of the nuclei, regulating gene silencing and plant traits. Natural and induced deletion of silencers upregulate expression of distal connected genes. Furthermore, we identify extensive allele-specific chromatin loops. We find that genetic variations alter allelic chromatin topology, thus modulating allelic gene imprinting in rice hybrids. In conclusion, the characterization of silencer-like regulatory elements and haplotype-resolved chromatin interaction maps provide insights into the understanding of molecular mechanisms underlying allelic gene silencing and plant trait controlling.
Display omitted
•H3K27me3 peak clusters may function as super silencer-like regulatory elements•Silencer-like regulatory elements regulate gene silencing via chromatin interactions•Deletion of silencers leads to chromatin loop disruption and gene upregulation•Allelic chromatin topology regulates allelic gene silencing in rice hybrids
By haplotype mapping of H3K27me3-associated chromatin interactions in rice hybrids, Ouyang et al. show that silencer-like regulatory elements regulate distal gene silencing by forming long-range chromatin interactions and find that genetic variations between the two parental alleles alter allelic chromatin topology and allele-specific gene silencing.
We have developed a novel machine-learning approach, MutPred Splice, for the identification of coding region substitutions that disrupt pre-mRNA splicing. Applying MutPred Splice to human ...disease-causing exonic mutations suggests that 16% of mutations causing inherited disease and 10 to 14% of somatic mutations in cancer may disrupt pre-mRNA splicing. For inherited disease, the main mechanism responsible for the splicing defect is splice site loss, whereas for cancer the predominant mechanism of splicing disruption is predicted to be exon skipping via loss of exonic splicing enhancers or gain of exonic splicing silencer elements. MutPred Splice is available at http://mutdb.org/mutpredsplice.
Neuroinflammation, as an important pathological characteristic of Parkinson's disease (PD), is primarily mediated by activated astrocytes and microglia. Neuron-restrictive silencer factor/repressor ...element 1 (RE1)-silencing transcription factor (NRSF/REST) regulates many genes and signal pathways involved in the inflammatory process in astrocytes. In the present study, we established the GFAP-Cre:NRSFflox/flox conditional knockout (cKO) mice. The expression of inflammation-associated molecules were measured in primary astrocytes from wild type (WT) and cKO mice after stimulation by 1-Methyl-4-phenylpyridine (MPP+), LPS, and conditioned medium (CM) of LPS-treated BV-2 microglial cells. The inflammatory molecule expression in BV-2 microglial cells exposed to conditioned medium of MPP+-treated primary astrocytes were also analyzed. Moreover, a subacute regimen of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride (MPTP) was used to establish mouse PD model and the damages to the nigrostriatal pathway were comprehensively evaluated in WT and cKO mice. We found that MPP+ induced a remarkable increase of NRSF expression in cultured astrocytes. Compared to WT astrocytes, the expression of inflammatory molecules IL-1β, IL-6, COX-2, and iNOS increased dramatically in NRSF deficient astrocytes challenged with CM of LPS-treated BV-2 cells. COX-2 and IL-1β transcripts were significantly elevated in BV-2 microglial cells exposed to CM of MPP+-treated NRSF deficient astrocytes compared to WT astrocytes. In cKO mice, the activation of astrocytes and microglial cells was more obvious, and the nigrostriatal dopaminergic system was more heavily injured compared to their WT counterparts after MPTP administration. Our results suggest that reactive NRSF deficient astrocytes orchestrated with microglial cells aggravate the pathophysiological progress in PD.
•Hyper-responses to CM of LPS-treated BV-2 cells in NRSF null astrocytes (AS).•Higher inflammatory responses to CM of MPP+-treated NRSF null AS in BV-2 cells.•More obvious activation of glial cells in MPTP-challenged cKO mice.•Severer damages to the nigrostriatal pathway in cKO mice after MPTP administration.
This paper aims to evaluate the potential of heat recovery from the integrated heat exchanger within the exhaust stack silencer baffles in a simple cycle gas turbine. Heat transfer channels were ...incorporated into the upstream (nose) and downstream (tail) sections of the parallel silencer baffles in the exhaust stack. The gas turbine exhaust gas represents the hot side flow across the baffles' sections. The integrated heat exchanger system offered an advantage of extracting waste heat from the exhaust stream, while reducing pressure drop on the flow and improving acoustic attenuation.
In this work, a series of parametric studies were carried out across a range of internal and external heat transfer area configurations within the silencers to maximize the heat transfer. Further enhancement opportunities were introduced and discussed based on the conducted parametric studies and practical aspects borne out of common industry practice. The proposed heat recovery system was implemented to power the gas fuel performance heater which is used to enhance the gas turbine cycle performance through utilization of the extracted waste heat while keeping lower exhaust pressure drop in the stack.
The obtained results showed that the proposed integrated heat exchanger within the silencers has a potential of generating a 5.48 MW net gain from the gas turbine exhaust stacks which are normally lost to the atmosphere from the simple cycle exhaust stack. The proposed heat recovery system proved significant fuel savings that lead to economic benefits and reduction in CO2 emissions.
Transcriptome studies are revealing that the eukaryotic genome actively transcribes a diverse repertoire of large noncoding RNAs (ncRNAs), many of which are unannotated and distinct from the small ...RNAs that have garnered much attention in recent years. Why are they so pervasive, and do they have a function? X-chromosome inactivation (XCI) is a classic epigenetic phenomenon associated with many large ncRNAs. Here, I provide a perspective on how XCI is achieved in mice and suggest how this knowledge can be applied to the rest of the genome. Emerging data indicate that long ncRNAs can function as guides and tethers, and may be the molecules of choice for epigenetic regulation: First, unlike proteins and small RNAs, large ncRNAs remain tethered to the site of transcription, and can therefore uniquely direct allelic regulation. Second, ncRNAs command a much larger sequence space than proteins, and can therefore achieve very precise spatiotemporal control of development. These properties imply that long noncoding transcripts may ultimately rival small RNAs and proteins in their versatility as epigenetic regulators, particularly for locus- and allele-specific control.
Aquaporin‐4, a predominant water channel in the central nervous system, has two isoforms, M1 and M23, whose transcripts are driven by distinct promoters. Using a reporter assay, we found that a ...fragment located between exons 0 and 1 of the mouse aquaporin‐4 gene, which had been thought to be the promoter for M23, lacked enhancers functioning in astrocytes. When the astrocyte‐specific enhancer (ASE) of the M1 promoter is connected to the putative M23 core promoter, it also works in astrocytes. Importantly, the ASE inhibits downstream promoter activity in NIH3T3 cells, indicating that the ASE also functions as a silencer in cells lacking aquaporin‐4.
Phages, viruses that prey on bacteria, are the most abundant and diverse inhabitants of the Earth. Temperate bacteriophages can integrate into the host genome and, as so-called prophages, maintain a ...long-term association with their host. The close relationship between host and virus has significantly shaped microbial evolution and phage elements may benefit their host by providing new functions. Nevertheless, the strong activity of phage promoters and potentially toxic gene products may impose a severe fitness burden and must be tightly controlled. In this context, xenogeneic silencing (XS) proteins, which can recognize foreign DNA elements, play an important role in the acquisition of novel genetic information and facilitate the evolution of regulatory networks. Currently known XS proteins fall into four classes (H-NS, MvaT, Rok and Lsr2) and have been shown to follow a similar mode of action by binding to AT-rich DNA and forming an oligomeric nucleoprotein complex that silences gene expression. In this review, we focus on the role of XS proteins in phage–host interactions by highlighting the important function of XS proteins in maintaining the lysogenic state and by providing examples of how phages fight back by encoding inhibitory proteins that disrupt XS functions in the host. Sequence analysis of available phage genomes revealed the presence of genes encoding Lsr2-type proteins in the genomes of phages infecting Actinobacteria. These data provide an interesting perspective for future studies to elucidate the impact of phage-encoded XS homologs on the phage life cycle and phage–host interactions.
Display omitted
•The activity of phages represents a major driver of horizontal gene transfer.•Xenogeneic silencing (XS) plays an important role in the silencing of foreign DNA.•XS proteins shape (pro-)phage–host interaction.•Phages employ multiple mechanisms to counteract XS.•Genome analysis revealed that actinophages encode different types of Lsr2-like proteins.
PDF
