Project description:Animal toxins are of interest to a wide range of scientists, due to their numerous applications in pharmacology, neurology, hematology, medicine, and drug research. This, and to a lesser extent the development of new performing tools in transcriptomics and proteomics, has led to an increase in toxin discovery. In this context, providing publicly available data on animal toxins has become essential. The UniProtKB/Swiss-Prot Tox-Prot program (http://www.uniprot.org/program/Toxins) plays a crucial role by providing such an access to venom protein sequences and functions from all venomous species. This program has up to now curated more than 5000 venom proteins to the high-quality standards of UniProtKB/Swiss-Prot (release 2012_02). Proteins targeted by these toxins are also available in the knowledgebase. This paper describes in details the type of information provided by UniProtKB/Swiss-Prot for toxins, as well as the structured format of the knowledgebase.
Project description:This SuperSeries is composed of the following subset Series: GSE36871: Nascent-Seq Reveals Novel Features of Mouse Circadian Transcriptional Regulation [RNA-Seq] GSE36872: Nascent-Seq Reveals Novel Features of Mouse Circadian Transcriptional Regulation [Nascent-Seq] GSE36873: Nascent-Seq Reveals Novel Features of Mouse Circadian Transcriptional Regulation [StrandSpe_NascentSeq] GSE36874: Nascent-Seq Reveals Novel Features of Mouse Circadian Transcriptional Regulation [ChIP-seq] Refer to individual Series
Project description:As a circadian organ, liver executes diverse functions in different phase of the circadian clock. This process is believed to be driven by a transcription program. Here, we present a TF DNA-binding activity centered multi-dimensional proteomics landscape, including DNA-binding activity of TFs, the phosphorylation pattern, ubiquitylation pattern, the nuclear sub-proteome, the whole proteome as well as the transcriptome, to portrait the hierarchical circadian clock network of mouse liver. The TF DNA-binding activity indicates diurnal oscillation in four major pathways, immune response, glucose metabolism, fatty acid metabolism, and the cell cycle. We also isolated the mouse liver Kupffer cells and measured their proteomes in the circadian clock to reveal cell type resolved circadian clock. These are the most comprehensive datasets for circadian clock in the mouse liver and provided the richest data resource for the understanding of mouse liver physiology around the circadian clock.
Project description:As a circadian organ, liver executes diverse functions in different phase of the circadian clock. This process is believed to be driven by a transcription program. Here, we present a TF DNA-binding activity centered multi-dimensional proteomics landscape, including DNA-binding activity of TFs, the phosphorylation pattern, ubiquitylation pattern, the nuclear sub-proteome, the whole proteome as well as the transcriptome, to portrait the hierarchical circadian clock network of mouse liver. The TF DNA-binding activity indicates diurnal oscillation in four major pathways, immune response, glucose metabolism, fatty acid metabolism, and the cell cycle. We also isolated the mouse liver Kupffer cells and measured their proteomes in the circadian clock to reveal cell type resolved circadian clock. These are the most comprehensive datasets for circadian clock in the mouse liver and provided the richest data resource for the understanding of mouse liver physiology around the circadian clock.
Project description:The mammalian circadian clock involves a transcriptional feedback loop in which CLOCK and BMAL1 activate the Period and Cryptochrome genes, which then feedback and repress their own transcription. We have interrogated the transcriptional architecture of the circadian transcriptional regulatory loop on a genome scale in mouse liver and find a stereotyped, time-dependent pattern of transcription factor binding, RNA polymerase II (RNAPII) recruitment, RNA expression and chromatin states. We find that the circadian transcriptional cycle of the clock consists of three distinct phases - a poised state, a coordinated de novo transcriptional activation state, and a repressed state. Interestingly only 22% of mRNA cycling genes are driven by de novo transcription, suggesting that both transcriptional and post-transcriptional mechanisms underlie the mammalian circadian clock. We also find that circadian modulation of RNAPII recruitment and chromatin remodeling occurs on a genome-wide scale far greater than that seen previously by gene expression profiling. Examination of 9 transcriptional regulators, 2 RNAPII and 6 histone modifications every 4hr during the circadian cycle in mouse liver
Project description:The circadian clock is a ubiquitous timekeeping system that organizes the behavior and physiology of organisms over the day and night. The clockwork orchestrates a multitude of metabolic processes as illustrated by previous global transcriptomics and proteomics studies, and the existence of daily rhythms of reduction and oxidation (redox) in a range of diverse species. However, the reciprocal question of whether metabolism can alter the clockwork remains largely unaddressed. Here we identify the pentose phosphate pathway (PPP), a critical source of cellular reducing power in the form of NADPH, as an important modulator of circadian oscillations. We show that genetic and pharmacologic inhibition of the PPP perturbs circadian gene expression and metabolic rhythms in human cells. Pharmacologic inhibition of the PPP caused similar effects in mouse tissues, and altered the pattern of rhythmic behavior in Drosophila. These manipulations also altered genome wide DNA-binding activity of the circadian transcription factors BMAL1 and CLOCK through a mechanism likely involving the redox-sensitive histone acetyltransferase p300. Thus, disruption of the PPP regulates circadian rhythms via modulation of NADPH metabolism, highlighting redox reactions as a novel connector of metabolic cycles and transcriptional oscillations in nucleated cells.
Project description:Exam change in the whole-cell and nuclear proteome circadian proteome in response to environmental circadian disruption (ECD) in mouse liver
Project description:BackgroundThe accuracy of protein 3D structure prediction has been dramatically improved with the help of advances in deep learning. In the recent CASP14, Deepmind demonstrated that their new version of AlphaFold (AF) produces highly accurate 3D models almost close to experimental structures. The success of AF shows that the multiple sequence alignment of a sequence contains rich evolutionary information, leading to accurate 3D models. Despite the success of AF, only the prediction code is open, and training a similar model requires a vast amount of computational resources. Thus, developing a lighter prediction model is still necessary.ResultsIn this study, we propose a new protein 3D structure modeling method, A-Prot, using MSA Transformer, one of the state-of-the-art protein language models. An MSA feature tensor and row attention maps are extracted and converted into 2D residue-residue distance and dihedral angle predictions for a given MSA. We demonstrated that A-Prot predicts long-range contacts better than the existing methods. Additionally, we modeled the 3D structures of the free modeling and hard template-based modeling targets of CASP14. The assessment shows that the A-Prot models are more accurate than most top server groups of CASP14.ConclusionThese results imply that A-Prot accurately captures the evolutionary and structural information of proteins with relatively low computational cost. Thus, A-Prot can provide a clue for the development of other protein property prediction methods.
Project description:Mammalian circadian rhythm is established by the negative feedback loops consisting of a set of clock genes, which lead to the circadian expression of thousands of downstream genes. As genome-wide transcription is organized under the high-order chromosome structure, it is unclear how circadian gene expression is influenced by chromosome structure. In this study, we focus on the function of chromatin structure proteins cohesin as well as CTCF (CCCTC-binding factor) in circadian rhythm. We analyzed the interactome of a Bmal1-bound enhancer upstream of a clock gene, Nr1d1, by 4C-seq and observed that cohesin binding sites are enriched in the interactome. Integrating circadian transcriptome data and cistrome data, we found that cohesin-CTCF co-binding sites tend to insulate the phases of circadian oscillating genes while cohesin-non-CTCF sites facilitate the interaction between circadian enhancer and promoter. A coarse-grained model integrating the long-range effect of cohesin and CTCF markedly improved our mechanistic understanding of circadian gene expression. This model is subsequently supported by our RNA-seq data from cohesin knockout cells. Cohesin is required at least in part for driving the circadian gene expression by facilitating the enhancer-promoter looping. Taken together, our study provided a novel insight into the relationship between circadian transcriptome and the high-order chromosome structure. Bmal1 ChIP-Seq in WT mouse embryonic fibroblast cells