13,079 research outputs found
Genome architecture and the role of transcription.
No full textDuring development or in response to environmental stimuli, eukaryotic genes change both their expression and position in 3D nuclear space. Then, is a gene transcribed because of its position, or is position determined by transcription? Are genes stochastically or deterministically engaged in transcription cycles? Recent results confirm that RNA polymerases and their transcription factors play central roles in genome organization, and that stochastic events can give rise to apparently deterministic expression. As is so often the case in biology, structure both determines function and is influenced by it
Television writer Peter Bowker in conversation with Professor John Cook
No full textPeter Bowker began his career working on Casualty, before going on to writesingle TV dramas such as the acclaimed Flesh and Blood (2002), about the sonof a couple with learning disabilities, and Eric and Ernie (2011), based on thestory of comedians Eric Morecambe and Ernie Wise. Bowker is also highly regarded for the series Blackpool (2004), a musical drama of six episodes starringDavid Morrissey as Ripley, which was influenced by the writing of DennisPotter, especially Pennies from Heaven and The Singing Detective
Exon skipping is correlated with exon circularization
No full textCircular RNAs are found in a wide range of organisms and it has been proposed that they perform disparate functions. However, how RNA circularization is connected to alternative splicing remains largely unexplored. Here, we stimulated primary human endothelial cells with tumor necrosis factor α or tumor growth factor β, purified RNA, generated >2.4 billion RNA-seq reads, and used a custom pipeline to characterize circular RNAs derived from coding exons. We find that circularization of exons is widespread and correlates with exon skipping, a feature that adds considerably to the regulatory complexity of the human transcriptome
Entropy-driven genome organization
No full textDNA and RNA polymerases active on bacterial and human genomes in the crowded environment of a cell are modeled as beads spaced along a string. Aggregation of the large polymerizing complexes increases the entropy of the system through an increase in entropy of the many small crowding molecules; this occurs despite the entropic costs of looping the intervening DNA. Results of a quantitative cost/benefit analysis are consistent with observations that active polymerases cluster into replication and transcription “factories” in both pro- and eukaryotes. We conclude that the second law of thermodynamics acts through nonspecific entropic forces between engaged polymerases to drive the self-organization of genomes into loops containing several thousands (and sometimes millions) of basepairs
Zechariah 9-14 as the substructure of 1 Peter’s eschatological program
No full textThe principal aim of this study is to discern what has shaped the author of 1 Peter to regard Christian suffering as a necessary (1.6) and to-be-expected (4.12) component of faithful allegiance to Jesus Christ. Most research regarding suffering in 1 Peter has limited the scope of inquiry to two particular aspects—its cause and nature, and the strategies that the author of 1 Peter employs in order to enable his addressees to respond in faithfulness. There remains, however, the need for a comprehensive explanation for the source that has generated 1 Peter’s theology of Christian suffering. If Jesus truly is the Christ, God’s chosen redemptive agent who has come to restore God’s people, then how can it be that Christian suffering is a necessary part of discipleship after his coming, death and resurrection? What led the author of 1 Peter to such a startling conclusion, which seems to runs against the grain of the eschatological hopes and expectations of Jewish restoration ideology?
This thesis analyzes the appropriation of shepherd and fiery trials imagery,
and argues that the author of 1 Peter is dependent upon Zechariah 9-14 for his
theology of Christian suffering. Said in another way, the eschatological program of
Zechariah 9-14, read through the lens of the Gospel, functions as the substructure
for 1 Peter’s eschatology and thus its theology of Christian suffering.
In support of this hypothesis, this study highlights the fact that Zechariah 9-
14 was available and appropriated in early Christianity, in particular in the Passion
Narrative tradition; that the shepherd imagery of 1 Pet 2.25 is best understood
within the milieu of the Passion Narrative tradition, and that it alludes to the
eschatological program of Zechariah 9-14; that the fiery trials imagery found in 1
Peter 1.6-7 and 1 Pet 4.12 is distinct from that which we find in Greco-Roman and OT
wisdom sources, and that it shares exclusive parallels with some unique features of
the eschatological program of Zechariah 9-14; that Zechariah 9-14 offers a more
satisfying explanation for the modification of Isa 11.2 in 1 Pet 4.14, the transition
from 4.12-19 to 5.1-4, why Peter has oriented his letter with the term διασπορά,
and why he has described his addresses as οἶκος τοῦ θεοῦ; and finally that 1 Peter
contains an implicit foundational narrative that shares distinct parallels with the
eschatological program of Zechariah 9-14.
We can conclude that 1 Peter offers a unique vista into the way in which at
least one early Christian witness came to understand and to communicate the fact
that Christian suffering was a necessary feature of faithful allegiance to Jesus Christ
Space exploration by the promoter of a long human gene during one transcription cycle
No full textAn RNA polymerase has been thought to transcribe by seeking out a promoter, initiating and then tracking down the template. We add tumor necrosis factor α to primary human cells, switch on transcription of a 221-kb gene and monitor promoter position during the ensuing transcription cycle (using RNA fluorescence in situ hybridization coupled to super-resolution localization, chromosome conformation capture and Monte Carlo simulations). Results are consistent with a polymerase immobilized in a 'factory' capturing a promoter and reeling in the template, as the transcript and promoter are extruded. Initially, the extruded promoter is tethered close to the factory and so likely to re-initiate; later, the tether becomes long enough to allow re-initiation in another factory. We suggest close tethering underlies enhancer function and transcriptional 'bursting'
Promoter type influences transcriptional topography by targeting genes to distinct nucleoplasmic sites.
No full textBoth the sequence of a promoter and the position of a gene in 3D nuclear space play crucial roles in gene regulation, but few studies address their inter-relationship. Using human and viral promoters on mini-chromosomes and RNA fluorescence in situ hybridization coupled to 'high-precision' localization, we show that promoters binding the same transcription factors and responding to the same signaling pathways tend to be co-transcribed in the same transcription factories. We go on to suggest how such spatial co-association might drive co-regulation of genes under the control of similar cis-elements
Dynamic reconfiguration of long human genes during one transcription cycle.
No full textWe analyzed three human genes that were >200 kbp in length as they are switched on rapidly and synchronously by tumor necrosis factor alpha and obtained new insights into the transcription cycle that are difficult to obtain using continuously active, short, genes. First, a preexisting "whole-gene" loop in one gene disappears on stimulation; it is stabilized by CCCTC-binding factor and TFIIB and poises the gene for a prompt response. Second, "subgene" loops (detected using chromosome conformation capture) develop and enlarge, a result that is simply explained if elongating polymerases become immobilized in transcription factories, where they reel in their templates. Third, high-resolution localization confirms that relevant nascent transcripts (detected using RNA fluorescence in situ hybridization) lie close enough to be present on the surface of one factory. These dynamics underscore the complex transitions between the poised, initiating, and elongating transcriptional states
Statistical phylogeographic tests of competing 'Lake Carpentaria hypotheses' in the mouth-brooding freshwater fish, Glossamia aprion (Apogonidae)
No full textGlacial cycles during the Pleistocene reduced sea levels and created new land connections in northern Australia, where many currently isolated rivers also became connected via an extensive paleo-lake system, ‘Lake Carpentaria’. However, the most recent period during which populations of freshwater species were connected by gene flow across Lake Carpentaria is debated: various ‘Lake Carpentaria hypotheses’ have been proposed. Here, we used a statistical phylogeographic approach to assess the timing of past population connectivity across the Carpentaria region in the obligate freshwater fish, Glossamia aprion. Results for this species indicate that the most recent period of genetic exchange across the Carpentaria region coincided with the mid- to late Pleistocene, a result shown previously for other freshwater and diadromous species. Based on these findings and published studies for various freshwater, diadromous and marine species, we propose a set of ‘Lake Carpentaria’ hypotheses to explain past population connectivity in aquatic species: (1) strictly freshwater species had widespread gene flow in the mid- to late Pleistocene before the last glacial maximum; (2) marine species were subdivided into eastern and western populations by land during Pleistocene glacial phases; and (3) past connectivity in diadromous species reflects the relative strength of their marine affinity.Benjamin D. Cook, Mark Adams, Peter B. Mather, and Jane M. Hughe
Revision2_Supplemental_Material_for_Fluid_walls_for_single-cell_monoclonality_by_Soitu_et_al – Supplemental material for Using Fluid Walls for Single-Cell Cloning Provides Assurance in Monoclonality
No full textSupplemental material, Revision2_Supplemental_Material_for_Fluid_walls_for_single-cell_monoclonality_by_Soitu_et_al for Using Fluid Walls for Single-Cell Cloning Provides Assurance in Monoclonality by Cristian Soitu, Cyril Deroy, Alfonso A. Castrejón-Pita, Peter R. Cook and Edmond J. Walsh in SLAS Technology</p
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