scholarly journals Cis-regulatory logic in the endo16 gene: switching from a specification to a differentiation mode of control

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 617-629 ◽  
Author(s):  
C.H. Yuh ◽  
H. Bolouri ◽  
E.H. Davidson
Keyword(s):  
Control System ◽  
Computational Model ◽  
Functional Organization ◽  
Regulatory Region ◽  
Regulatory System ◽  
Functional Change ◽  
Proximal Region ◽  
Transcription Factor Target ◽  
System Module ◽  
Logic Operations

The endo16 gene of Strongylocentrotus purpuratus encodes a secreted protein of the embryonic and larval midgut. The overall functional organization of the spatial and temporal control system of this gene are relatively well known from a series of earlier cis-regulatory studies. Our recent computational model for the logic operations of the proximal region of the endo16 control system (Module A) specifies the function of interactions at each transcription factor target site of Module A. Here, we extend sequence level functional analysis to the adjacent cis-regulatory region, Module B. The computational logic model is broadened to include B/A interactions as well as other Module B functions. Module B drives expression later in development and its major activator is responsible for a sharp, gut-specific increase in transcription after gastrulation. As shown earlier, Module B output undergoes a synergistic amplification that requires interactions within Module A. The interactions within Module B that are required to generate and transmit its output to Module A are identified. Logic considerations predicted an internal cis-regulatory switch by which spatial control of endo16 expression is shifted from Module A (early) to Module B (later). This prediction was confirmed experimentally and a distinct set of interactions in Module B that mediate the switch function was demonstrated. The endo16 computational model now provides a detailed explanation of the information processing functions executed by the cis-regulatory system of this gene throughout embryogenesis. Early in development the gene participates in the specification events that define the endomesoderm; later it functions as a gut-specific differentiation gene. The cis-regulatory switch mediates this functional change.

scholarly journals Spatial and temporal information processing in the sea urchin embryo: modular and intramodular organization of the CyIIIa gene cis-regulatory system

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 333-348 ◽  
Author(s):  
C.V. Kirchhamer ◽  
E.H. Davidson
Keyword(s):  
Transcription Factors ◽  
Functional Organization ◽  
Specific Interaction ◽  
Regulatory Region ◽  
Regulatory System ◽  
Dna Interaction ◽  
Regulatory Function ◽  
Regulatory Structure ◽  
Spatial Expression ◽  
Target Sites

The CyIIIa cytoskeletal actin gene of Strongylocentrotus purpuratus is expressed specifically in the aboral ectoderm. In earlier work we identified a 2.3 kb cis-regulatory region that is necessary and sufficient for correct spatial and temporal expression of a CyIIIa.CAT gene. This region includes about 20 sites of specific protein-DNA interaction, at which at least nine different transcription factors may be bound. All except two of these factors have been cloned. In this work we have analyzed by deletion or mutagenesis each specific interaction. A specific function was identified for every binding site examined. These individual functions include control of amplitude and timing of expression at different phases of embryogenesis, and control of spatial expression. We show that particular negative regulatory interactions are required to repress expression of the CyIIIa.CAT construct in oral ectoderm and in skeletogenic mesenchyme at different stages. In further experiments we determined the overall functional organization of the CyIIIa cis-regulatory system, and we show that this system is modular in its regulatory structure. The ‘proximal module’ (with respect to the transcription start site) extends upstream for about 800 base pairs, and includes nine target sites serviced by six different transcription factors. Its major role is to establish CyIIIa expression in the aboral ectoderm territory as the blastomere founder cells are specified and the oral-aboral axis is determined, and to activate the CyIIIa gene late in cleavage. The ‘middle module,’ which lies upstream of the proximal module, acquires major control of CyIIIa function after the blastula stage. It includes six target sites, serviced by four different factors. The middle module is responsible for a sharp increase in expression occurring during gastrulation, mediated by the positively acting factors that bind within it. The middle module also includes sites at which two different negatively acting spatial control factors bind, the functions of which are required for correct spatial expression late in embryogenesis. The ‘distal module’ contains a number of sites at which a positively acting factor binds, but this module exercises no spatial regulatory function. Interactions within the distal module are required for the normal levels of function of both the proximal and middle modules.

scholarly journals Transvection at the End of the Truncated Chromosome in Drosophila melanogaster

Genetics ◽  
2003 ◽  
Vol 163 (4) ◽  
pp. 1375-1387
Author(s):  
Mikhail Savitsky ◽  
Tatyana Kahn ◽  
Ekaterina Pomerantseva ◽  
Pavel Georgiev
Keyword(s):  
Drosophila Melanogaster ◽  
Homologous Chromosome ◽  
Regulatory Region ◽  
Proximal Region ◽  
The Other ◽  
Upstream Region ◽  
Upstream Sequence ◽  
Transcription Start ◽  
Promoter Proximal Region

Abstract The phenomenon of transvection is well known for the Drosophila yellow locus. Thus enhancers of a promoterless yellow locus in one homologous chromosome can activate the yellow promoter in the other chromosome where the enhancers are inactive or deleted. In this report, we examined the requirements for trans-activation of the yellow promoter at the end of the deficient chromosome. A number of truncated chromosomes ending in different areas of the yellow regulatory region were examined in combination with the promoterless y alleles. We found that trans-activation of the yellow promoter at the end of a deficient chromosome required ∼6 kb of an additional upstream sequence. The nature of upstream sequences affected the strength of transvection: addition of gypsy sequences induced stronger trans-activation than addition of HeT-A or yellow sequences. Only the promoter proximal region (within -158 bp of the yellow transcription start) was essential for trans-activation; i.e., transvection did not require extensive homology in the yellow upstream region. Finally, the yellow enhancers located on the two pairing chromosomes could cooperatively activate one yellow promoter.

Legalising the Drug Wars

2021 ◽  
Author(s):  
John Collins
Keyword(s):  
Control System ◽  
Focal Point ◽  
Regulatory System ◽  
Legal Framework ◽  
Drug Control ◽  
Global Policy ◽  
Drug Regulations ◽  
Single Convention ◽  
History Of ◽  
Narcotic Drugs

Where did the regulatory underpinnings for the global drug wars come from? This book is the first fully-focused history of the 1961 UN Single Convention on Narcotic Drugs, the bedrock of the modern multilateral drug control system and the focal point of global drug regulations and prohibitions. Although far from the propagator of the drug wars, the UN enabled the creation of a uniform global legal framework to effectively legalise, or regulate, their pursuit. This book thereby answers the question of where the international legal framework for drug control came from, what state interests informed its development and how complex diplomatic negotiations resulted in the current regulatory system, binding states into an element of global policy uniformity.

scholarly journals Identification of theVERNALIZATION 4gene reveals the origin of spring growth habit in ancient wheats from South Asia

2015 ◽  
Vol 112 (39) ◽  
pp. E5401-E5410 ◽  
Author(s):  
Nestor Kippes ◽  
Juan M. Debernardi ◽  
Hans A. Vasquez-Gross ◽  
Bala A. Akpinar ◽  
Hikment Budak ◽  
...  
Keyword(s):  
South Asia ◽  
Rna Binding ◽  
Growth Habit ◽  
Regulatory Region ◽  
Proximal Region ◽  
Induced Mutations ◽  
Wheat Varieties ◽  
Density Mapping ◽  
Chromosome Arm ◽  
Delayed Flowering

Wheat varieties with a winter growth habit require long exposures to low temperatures (vernalization) to accelerate flowering. Natural variation in four vernalization genes regulating this requirement has favored wheat adaptation to different environments. The first three genes (VRN1–VRN3) have been cloned and characterized before. Here we show that the fourth gene,VRN-D4, originated by the insertion of a ∼290-kb region from chromosome arm 5AL into the proximal region of chromosome arm 5DS. The inserted 5AL region includes a copy ofVRN-A1that carries distinctive mutations in its coding and regulatory regions. Three lines of evidence confirmed that this gene isVRN-D4: it cosegregated withVRN-D4in a high-density mapping population; it was expressed earlier than otherVRN1genes in the absence of vernalization; and induced mutations in this gene resulted in delayed flowering.VRN-D4was found in most accessions of the ancient subspeciesTriticum aestivumssp.sphaerococcumfrom South Asia. This subspecies showed a significant reduction of genetic diversity and increased genetic differentiation in the centromeric region of chromosome 5D, suggesting thatVRN-D4likely contributed to local adaptation and was favored by positive selection. Three adjacent SNPs in a regulatory region of theVRN-D4first intron disrupt the binding ofGLYCINE-RICH RNA-BINDING PROTEIN 2(TaGRP2), a known repressor ofVRN1expression. The same SNPs were identified inVRN-A1alleles previously associated with reduced vernalization requirement. These alleles can be used to modulate vernalization requirements and to develop wheat varieties better adapted to different or changing environments.

scholarly journals Modernizing Conceptions of Valuation and Cognitive-Control Deployment in Adolescent Risk Taking

2019 ◽  
Vol 29 (1) ◽  
pp. 102-109 ◽  
Author(s):  
Kathy T. Do ◽  
Paul B. Sharp ◽  
Eva H. Telzer
Keyword(s):  
Decision Making ◽  
Control System ◽  
Cognitive Control ◽  
Computational Model ◽  
Risk Taking ◽  
Expected Value ◽  
Risky Decision Making ◽  
Risky Decision ◽  
Adolescent Risk ◽  
Risk Taking Behavior

Heightened risk taking in adolescence has long been attributed to valuation systems overwhelming the deployment of cognitive control. However, this explanation of why adolescents engage in risk taking is insufficient given increasing evidence that risk-taking behavior can be strategic and involve elevated cognitive control. We argue that applying the expected-value-of-control computational model to adolescent risk taking can clarify under what conditions control is elevated or diminished during risky decision-making. Through this lens, we review research examining when adolescent risk taking might be due to—rather than a failure of—effective cognitive control and suggest compelling ways to test such hypotheses. This effort can resolve when risk taking arises from an immaturity of the control system itself, as opposed to arising from differences in what adolescents value relative to adults. It can also identify promising avenues for channeling cognitive control toward adaptive outcomes in adolescence.

scholarly journals Transcription of the Streptococcus pyogenes Hyaluronic Acid Capsule Biosynthesis Operon Is Regulated by Previously Unknown Upstream Elements

2014 ◽  
Vol 82 (12) ◽  
pp. 5293-5307 ◽  
Author(s):  
Marina Falaleeva ◽  
Oliwia W. Zurek ◽  
Robert L. Watkins ◽  
Robert W. Reed ◽  
Hadeel Ali ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Streptococcus Pyogenes ◽  
Regulatory Region ◽  
Regulatory System ◽  
Invasive Disease ◽  
Negative Regulator ◽  
Mobility Shift ◽  
Putative Promoter ◽  
Transcriptional Terminator ◽  
Content Type

ABSTRACTThe important human pathogenStreptococcus pyogenes(group AStreptococcus[GAS]) produces a hyaluronic acid (HA) capsule that plays critical roles in immune evasion. Previous studies showed that thehasABCoperon encoding the capsule biosynthesis enzymes is under the control of a single promoter, P1, which is negatively regulated by the two-component regulatory system CovR/S. In this work, we characterize the sequence upstream of P1 and identify a novel regulatory region controlling transcription of the capsule biosynthesis operon in the M1 serotype strain MGAS2221. This region consists of a promoter, P2, which initiates transcription of a novel small RNA, HasS, an intrinsic transcriptional terminator that inefficiently terminates HasS, permitting read-through transcription ofhasABC, and a putative promoter which lies upstream of P2. Electrophoretic mobility shift assays, quantitative reverse transcription-PCR, and transcriptional reporter data identified CovR as a negative regulator of P2. We found that the P1 and P2 promoters are completely repressed by CovR, and capsule expression is regulated by the putative promoter upstream of P2. Deletion ofhasSor of the terminator eliminates CovR-binding sequences, relieving repression and increasing read-through,hasAtranscription, and capsule production. Sequence analysis of 44 GAS genomes revealed a high level of polymorphism in the HasS sequence region. Most of the HasS variations were located in the terminator sequences, suggesting that this region is under strong selective pressure. We discovered that the terminator deletion mutant is highly resistant to neutrophil-mediated killing and is significantly more virulent in a mouse model of GAS invasive disease than the wild-type strain. Together, these results are consistent with the naturally occurring mutations in this region modulating GAS virulence.

scholarly journals Polymyxin B Resistance and Biofilm Formation in Vibrio cholerae Are Controlled by the Response Regulator CarR

2015 ◽  
Vol 83 (3) ◽  
pp. 1199-1209 ◽  
Author(s):  
Kivanc Bilecen ◽  
Jiunn C. N. Fong ◽  
Andrew Cheng ◽  
Christopher J. Jones ◽  
David Zamorano-Sánchez ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Biofilm Formation ◽  
Lipid A ◽  
Response Regulator ◽  
Regulatory Region ◽  
Regulatory System ◽  
Polymyxin B ◽  
Content Type ◽  
Two Component ◽  
Antimicrobial Peptide Resistance

Two-component systems play important roles in the physiology of many bacterial pathogens.Vibrio cholerae's CarRS two-component regulatory system negatively regulates expression ofvps(Vibriopolysaccharide) genes and biofilm formation. In this study, we report that CarR confers polymyxin B resistance by positively regulating expression of thealmEFGgenes, whose products are required for glycine and diglycine modification of lipid A. We determined that CarR directly binds to the regulatory region of thealmEFGoperon. Similarly to acarRmutant, strains lackingalmE,almF, andalmGexhibited enhanced polymyxin B sensitivity. We also observed that strains lackingalmEor thealmEFGoperon have enhanced biofilm formation. Our results reveal that CarR regulates biofilm formation and antimicrobial peptide resistance inV. cholerae.

ASTRA1 solid state star trackers for Martin Marietta's modular attitude control system module

1993 ◽  
Author(s):  
Sarma N. Gullapalli ◽  
David J. Flynn ◽  
Frank J. Kissh ◽  
Albert G. Gauthier ◽  
Thomas M. Kenney
Keyword(s):  
Control System ◽  
Solid State ◽  
Attitude Control ◽  
Attitude Control System ◽  
System Module

Bacterioferritin: Properties, structural and functional organization of the dps gene regulatory region

BIOPHYSICS ◽  
2011 ◽  
Vol 56 (5) ◽  
pp. 795-802 ◽  
Author(s):  
U. S. Shvyreva ◽  
M. N. Tutukina ◽  
O. N. Ozoline
Keyword(s):  
Functional Organization ◽  
Regulatory Region ◽  
Gene Regulatory

scholarly journals A Novel Class of Heat and Secretion Stress-Responsive Genes Is Controlled by the Autoregulated CssRS Two-Component System of Bacillus subtilis

2002 ◽  
Vol 184 (20) ◽  
pp. 5661-5671 ◽  
Author(s):  
Elise Darmon ◽  
David Noone ◽  
Anne Masson ◽  
Sierd Bron ◽  
Oscar P. Kuipers ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Heat Stress ◽  
Transcriptional Activation ◽  
Cellular Response ◽  
Regulatory Region ◽  
Regulatory System ◽  
Secretion Stress ◽  
Two Component ◽  
High Level ◽  
Inducible Genes

ABSTRACT Bacteria need dedicated systems that allow appropriate adaptation to the perpetual changes in their environments. In Bacillus subtilis, two HtrA-like proteases, HtrA and HtrB, play critical roles in the cellular response to secretion and heat stresses. Transcription of these genes is induced by the high-level production of a secreted protein or by a temperature upshift. The CssR-CssS two-component regulatory system plays an essential role in this transcriptional activation. Transcription of the cssRS operon is autoregulated and can be induced by secretion stress, by the absence of either HtrA or HtrB, and by heat stress in a HtrA null mutant strain. Two start sites are used for cssRS transcription, only one of which is responsive to heat and secretion stress. The divergently transcribed htrB and cssRS genes share a regulatory region through which their secretion and heat stress-induced expression is linked. This study shows that CssRS-regulated genes represent a novel class of heat-inducible genes, which is referred to as class V and currently includes two genes: htrA and htrB.

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