A cell cycle-coordinated Polymerase II transcription compartment encompasses gene expression before global genome activation
TL;DR: It is proposed, that the transcription compartment is part of the regulatory architecture of embryonic nuclei and offers a transcriptionally competent environment to facilitate early escape from repression before global genome activation.
Abstract: Most metazoan embryos commence development with rapid, transcriptionally silent cell divisions, with genome activation delayed until the mid-blastula transition (MBT). However, a set of genes escapes global repression and gets activated before MBT. Here we describe the formation and the spatio-temporal dynamics of a pair of distinct transcription compartments, which encompasses the earliest gene expression in zebrafish. 4D imaging of pri-miR430 and zinc-finger-gene activities by a novel, native transcription imaging approach reveals transcriptional sharing of nuclear compartments, which are regulated by homologous chromosome organisation. These compartments carry the majority of nascent-RNAs and active Polymerase II, are chromatin-depleted and represent the main sites of detectable transcription before MBT. Transcription occurs during the S-phase of increasingly permissive cleavage cycles. It is proposed, that the transcription compartment is part of the regulatory architecture of embryonic nuclei and offers a transcriptionally competent environment to facilitate early escape from repression before global genome activation. Transcription is globally repressed in early stage of embryo development, but a set of genes including pri-miR-430 and zinc finger genes is known to escape the repression. Here the authors image the very first transcriptional activities in the living zebra fish embryo, demonstrating a cell cycle-coordinated polymerase II transcription compartment.
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14 Sep 2020
TL;DR: In this article, the authors consider key factors contributing to this issue, explore how federated learning may provide a solution for the future of digital health and highlight the challenges and considerations that need to be addressed.
Abstract: Data-driven machine learning (ML) has emerged as a promising approach for building accurate and robust statistical models from medical data, which is collected in huge volumes by modern healthcare systems. Existing medical data is not fully exploited by ML primarily because it sits in data silos and privacy concerns restrict access to this data. However, without access to sufficient data, ML will be prevented from reaching its full potential and, ultimately, from making the transition from research to clinical practice. This paper considers key factors contributing to this issue, explores how federated learning (FL) may provide a solution for the future of digital health and highlights the challenges and considerations that need to be addressed.
606 citations
Journal Article•
TL;DR: A strategy to measure the timing of DNA replication for thousands of genes in a single DNA array hybridization experiment generated a genome-wide map of replication timing for Drosophila melanogaster and found a strong correlation between DNA replication early in S phase and transcriptional activity.
Abstract: Replication of the genome before mitotic cell division is a highly regulated process that ensures the fidelity of DNA duplication. DNA replication initiates at specific locations, termed origins of replication, and progresses in a defined temporal order during the S phase of the cell cycle. The relationship between replication timing and gene expression has been the subject of some speculation. A recent genome-wide analysis in Saccharomyces cerevisiae showed no association between replication timing and gene expression. In higher eukaryotes, the limited number of genomic loci analyzed has not permitted a firm conclusion regarding this association. To explore the relationship between DNA replication and gene expression in higher eukaryotes, we developed a strategy to measure the timing of DNA replication for thousands of genes in a single DNA array hybridization experiment. Using this approach, we generated a genome-wide map of replication timing for Drosophila melanogaster. Moreover, by surveying over 40% of all D. melanogaster genes, we found a strong correlation between DNA replication early in S phase and transcriptional activity. As this correlation does not exist in S. cerevisiae, this interplay between DNA replication and transcription may be a unique characteristic of higher eukaryotes.
321 citations
TL;DR: Current understanding of the mechanisms that underlie handover of developmental control to the zygotic genome during the maternal-to-zygotic transition is reviewed.
Abstract: The development of animal embryos is initially directed by maternal gene products. Then, during the maternal-to-zygotic transition (MZT), developmental control is handed to the zygotic genome. Extensive research in both vertebrate and invertebrate model organisms has revealed that the MZT can be subdivided into two phases, during which very different modes of gene regulation are implemented: initially, regulation is exclusively post-transcriptional and post-translational, following which gradual activation of the zygotic genome leads to predominance of transcriptional regulation. These changes in the gene expression program of embryos are precisely controlled and highly interconnected. Here, we review current understanding of the mechanisms that underlie handover of developmental control during the MZT.
231 citations
Cites background from "A cell cycle-coordinated Polymerase..."
...What is clear, is that cell cycle length affects the length and number of transcripts that are produced in Drosophila and zebrafish embryos (Edgar and Schubiger, 1986; Hadzhiev et al., 2019; Rothe et al., 1992; Dalle Nogare et al., 2009)....
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...In this context, it is interesting to note that, in Drosophila and zebrafish, zygotic transcription begins in two distinct areas in the nucleus (Blythe and Wieschaus, 2016; Chan et al., 2018 preprint; Chen et al., 2013; Hadzhiev et al., 2019; Hilbert et al., 2018 preprint; Hug et al., 2017), which may cause a local increase in the concentration of transcription factors, thereby facilitating transcription....
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...elegans, Xenopus, zebrafish and Drosophila, the first zygotic transcripts are detected in cell cycles 2, 3, 6 and 8, respectively (Chan et al., 2018 preprint; Collart et al., 2014; De Renzis et al., 2007; Edgar et al., 1994; Hadzhiev et al., 2019; Heyn et al., 2014; Hilbert et al., 2018 preprint; Kimelman et al., 1987; Kwasnieski et al., 2019 preprint; Lécuyer et al., 2007; Lott et al., 2011; Mathavan et al., 2005; Owens et al., 2016; Paranjpe et al., 2013; Seydoux and Fire, 1994; Skirkanich et al., 2011; Tan et al., 2013; Yanai et al., 2011; Yang et al., 2002), although there is some genetic evidence that transcription may begin earlier in Drosophila (Ali-Murthy et al....
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TL;DR: A critical review on how polyoxometalates emerged from being molecular clusters for fundamental studies, to next-generation materials for energy applications is provided in this article, highlighting how exploiting the versatility and activity of these molecules can lead to improved performance in energy devices such as supercapacitors and batteries, and in energy catalyst applications.
Abstract: Polyoxometalates (POMs) represent a class of nanomaterials, which hold enormous promise for a range of energy-related applications. Their promise is owing to their “special” structure that gives POMs a truly unique ability to control redox reactions in energy conversion and storage. One such amazing capability is their large number of redox active sites that arises from the complex three-dimensional cluster of metal-oxide ions linked together by oxygen atoms. Here, a critical review on how POMs emerged from being molecular clusters for fundamental studies, to next-generation materials for energy applications is provided. We highlight how exploiting the versatility and activity of these molecules can lead to improved performance in energy devices such as supercapacitors and batteries, and in energy catalyst applications. The potential of POMs across numerous fields is systematically outlined by investigating structure–property–performance relationships and the determinant factors for energy systems. Finally, the challenges and opportunities for this class of materials with respect to addressing our pressing energy-related concerns are identified.
126 citations
TL;DR: With 2.5 global hectares (gha) per capita against 2.7 gha per capita, China's ecological footprint is desirably below the world's average ecological footprint per capita as discussed by the authors.
Abstract: With 2.5 global hectares (gha) per capita against 2.7 gha per capita, China’s ecological footprint is desirably below the world’s average ecological footprint per capita. Undesirably, the country’s...
124 citations
References
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TL;DR: MUSCLE is a new computer program for creating multiple alignments of protein sequences that includes fast distance estimation using kmer counting, progressive alignment using a new profile function the authors call the log-expectation score, and refinement using tree-dependent restricted partitioning.
Abstract: We describe MUSCLE, a new computer program for creating multiple alignments of protein sequences. Elements of the algorithm include fast distance estimation using kmer counting, progressive alignment using a new profile function we call the logexpectation score, and refinement using treedependent restricted partitioning. The speed and accuracy of MUSCLE are compared with T-Coffee, MAFFT and CLUSTALW on four test sets of reference alignments: BAliBASE, SABmark, SMART and a new benchmark, PREFAB. MUSCLE achieves the highest, or joint highest, rank in accuracy on each of these sets. Without refinement, MUSCLE achieves average accuracy statistically indistinguishable from T-Coffee and MAFFT, and is the fastest of the tested methods for large numbers of sequences, aligning 5000 sequences of average length 350 in 7 min on a current desktop computer. The MUSCLE program, source code and PREFAB test data are freely available at http://www.drive5. com/muscle.
37,524 citations
TL;DR: The Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure outperforms other aligners by a factor of >50 in mapping speed.
Abstract: Motivation Accurate alignment of high-throughput RNA-seq data is a challenging and yet unsolved problem because of the non-contiguous transcript structure, relatively short read lengths and constantly increasing throughput of the sequencing technologies. Currently available RNA-seq aligners suffer from high mapping error rates, low mapping speed, read length limitation and mapping biases. Results To align our large (>80 billon reads) ENCODE Transcriptome RNA-seq dataset, we developed the Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure. STAR outperforms other aligners by a factor of >50 in mapping speed, aligning to the human genome 550 million 2 × 76 bp paired-end reads per hour on a modest 12-core server, while at the same time improving alignment sensitivity and precision. In addition to unbiased de novo detection of canonical junctions, STAR can discover non-canonical splices and chimeric (fusion) transcripts, and is also capable of mapping full-length RNA sequences. Using Roche 454 sequencing of reverse transcription polymerase chain reaction amplicons, we experimentally validated 1960 novel intergenic splice junctions with an 80-90% success rate, corroborating the high precision of the STAR mapping strategy. Availability and implementation STAR is implemented as a standalone C++ code. STAR is free open source software distributed under GPLv3 license and can be downloaded from http://code.google.com/p/rna-star/.
30,684 citations
TL;DR: The TopHat pipeline is much faster than previous systems, mapping nearly 2.2 million reads per CPU hour, which is sufficient to process an entire RNA-Seq experiment in less than a day on a standard desktop computer.
Abstract: Motivation: A new protocol for sequencing the messenger RNA in a cell, known as RNA-Seq, generates millions of short sequence fragments in a single run. These fragments, or ‘reads’, can be used to measure levels of gene expression and to identify novel splice variants of genes. However, current software for aligning RNA-Seq data to a genome relies on known splice junctions and cannot identify novel ones. TopHat is an efficient read-mapping algorithm designed to align reads from an RNA-Seq experiment to a reference genome without relying on known splice sites.
Results: We mapped the RNA-Seq reads from a recent mammalian RNA-Seq experiment and recovered more than 72% of the splice junctions reported by the annotation-based software from that study, along with nearly 20 000 previously unreported junctions. The TopHat pipeline is much faster than previous systems, mapping nearly 2.2 million reads per CPU hour, which is sufficient to process an entire RNA-Seq experiment in less than a day on a standard desktop computer. We describe several challenges unique to ab initio splice site discovery from RNA-Seq reads that will require further algorithm development.
Availability: TopHat is free, open-source software available from http://tophat.cbcb.umd.edu
Contact: ude.dmu.sc@eloc
Supplementary information: Supplementary data are available at Bioinformatics online.
11,473 citations
TL;DR: How BLAT was optimized is described, which is more accurate and 500 times faster than popular existing tools for mRNA/DNA alignments and 50 times faster for protein alignments at sensitivity settings typically used when comparing vertebrate sequences.
Abstract: Analyzing vertebrate genomes requires rapid mRNA/DNA and cross-species protein alignments A new tool, BLAT, is more accurate and 500 times faster than popular existing tools for mRNA/DNA alignments and 50 times faster for protein alignments at sensitivity settings typically used when comparing vertebrate sequences BLAT's speed stems from an index of all nonoverlapping K-mers in the genome This index fits inside the RAM of inexpensive computers, and need only be computed once for each genome assembly BLAT has several major stages It uses the index to find regions in the genome likely to be homologous to the query sequence It performs an alignment between homologous regions It stitches together these aligned regions (often exons) into larger alignments (typically genes) Finally, BLAT revisits small internal exons possibly missed at the first stage and adjusts large gap boundaries that have canonical splice sites where feasible This paper describes how BLAT was optimized Effects on speed and sensitivity are explored for various K-mer sizes, mismatch schemes, and number of required index matches BLAT is compared with other alignment programs on various test sets and then used in several genome-wide applications http://genomeucscedu hosts a web-based BLAT server for the human genome
8,326 citations
TL;DR: Jalview 2 is a system for interactive WYSIWYG editing, analysis and annotation of multiple sequence alignments that employs web services for sequence alignment, secondary structure prediction and the retrieval of alignments, sequences, annotation and structures from public databases and any DAS 1.53 compliant sequence or annotation server.
Abstract: Summary: Jalview Version 2 is a system for interactive WYSIWYG editing, analysis and annotation of multiple sequence alignments. Core features include keyboard and mouse-based editing, multiple views and alignment overviews, and linked structure display with Jmol. Jalview 2 is available in two forms: a lightweight Java applet for use in web applications, and a powerful desktop application that employs web services for sequence alignment, secondary structure prediction and the retrieval of alignments, sequences, annotation and structures from public databases and any DAS 1.53 compliant sequence or annotation server.
Availability: The Jalview 2 Desktop application and JalviewLite applet are made freely available under the GPL, and can be downloaded from www.jalview.org
Contact: g.j.barton@dundee.ac.uk
7,926 citations