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https://www.readbyqxmd.com/read/28333240/structure-of-the-transcriptional-regulatory-network-correlates-with-regulatory-divergence-in-drosophila
#1
Bing Yang, Patricia J Wittkopp
Transcriptional control of gene expression is regulated by biochemical interactions between cis-regulatory DNA sequences and trans-acting factors that form complex regulatory networks. Genetic changes affecting both cis- and trans-acting sequences in these networks have been shown to alter patterns of gene expression as well as higher-order organismal phenotypes. Here, we investigate how the structure of these regulatory networks relates to patterns of polymorphism and divergence in gene expression. To do this, we compared a transcriptional regulatory network inferred for Drosophila melanogaster to differences in gene regulation observed between two strains of D...
February 25, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28332702/the-mtp1-promoters-from-arabidopsis-halleri-reveal-cis-regulating-elements-for-the-evolution-of-metal-tolerance
#2
Elisa Fasani, Giovanni DalCorso, Claudio Varotto, Mingai Li, Giovanna Visioli, Monica Mattarozzi, Antonella Furini
In the hyperaccumulator Arabidopsis halleri, the zinc (Zn) vacuolar transporter MTP1 is a key component of hypertolerance. Because protein sequences and functions are highly conserved between A. halleri and Arabidopsis thaliana, Zn tolerance in A. halleri may reflect the constitutively higher MTP1 expression compared with A. thaliana, based on copy number expansion and different cis regulation. Three MTP1 promoters were characterized in A. halleri ecotype I16. The comparison with the A. thaliana MTP1 promoter revealed different expression profiles correlated with specific cis-acting regulatory elements...
March 23, 2017: New Phytologist
https://www.readbyqxmd.com/read/28320880/rna-mediated-cis-regulation-in-acinetobacter-baumannii-modulates-stress-induced-phenotypic-variation
#3
Carly Ching, Kevin Gozzi, Björn Heinemann, Yunrong Chai, Veronica G Godoy
In the nosocomial opportunistic pathogen Acinetobacter baumannii, RecA-dependent mutagenesis, which causes antibiotic resistance acquisition, is linked to the DNA damage response (DDR). Notably, unlike the Escherichia coli paradigm, recA and DDR gene expression in A. baumannii are bimodal. Namely, there is phenotypic variation upon DNA damage, which may provide a bet-hedging strategy for survival. Thus, understanding recA gene regulation is key to elucidate the yet unknown DDR regulation in A. baumannii Here, we identify a structured 5' Untranslated Region (5' UTR) in the recA transcript which serves as a cis-regulatory element...
March 20, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28166241/evolutionary-analysis-reveals-regulatory-and-functional-landscape-of-coding-and-non-coding-rna-editing
#4
Rui Zhang, Patricia Deng, Dionna Jacobson, Jin Billy Li
Adenosine-to-inosine RNA editing diversifies the transcriptome and promotes functional diversity, particularly in the brain. A plethora of editing sites has been recently identified; however, how they are selected and regulated and which are functionally important are largely unknown. Here we show the cis-regulation and stepwise selection of RNA editing during Drosophila evolution and pinpoint a large number of functional editing sites. We found that the establishment of editing and variation in editing levels across Drosophila species are largely explained and predicted by cis-regulatory elements...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28115635/body-hypomethylated-human-genes-harbor-extensive-intragenic-transcriptional-activity-and-are-prone-to-cancer-associated-dysregulation
#5
Isabel Mendizabal, Jia Zeng, Thomas E Keller, Soojin V Yi
Genomic DNA methylation maps (methylomes) encode genetic and environmental effects as stable chemical modifications of DNA. Variations in DNA methylation, especially in regulatory regions such as promoters and enhancers, are known to affect numerous downstream processes. In contrast, most transcription units (gene bodies) in the human genome are thought to be heavily methylated. However, epigenetic reprogramming in cancer often involves gene body hypomethylation with consequences on gene expression. In this study, we focus on the relatively unexplored phenomenon that some gene bodies are devoid of DNA methylation under normal conditions...
January 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28035386/microduplication-of-7q36-3-encompassing-the-shh-long%C3%A2-range-regulator-zrs-in-a-patient-with-triphalangeal-thumb%C3%A2-polysyndactyly-syndrome-and-congenital-heart-disease
#6
Zhenghua Liu, Ni Yin, Lianghui Gong, Zhiping Tan, Bangliang Yin, Yifeng Yang, Cheng Luo
Triphalangeal thumb‑polysyndactyly syndrome (TPT‑PS) is an autosomal dominant disorder with complete penetrance and a variable expression consisting of opposable triphalangeal thumbs, duplication of the distal thumb phalanx, pre‑axial polydactyly and duplication of the big toes (hallux). The causative gene of TPT‑PS has been mapped to 7q36.3. Sonic hedgehog (SHH) expressed in the zone of polarizing activity (ZPA) has an important role in defining the anterior‑posterior axis and numbers of digits in limb bud development...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28027852/analyses-of-differentially-expressed-genes-after-exposure-to-acute-stress-acute-ethanol-or-a-combination-of-both-in-mice
#7
Jessica A Baker, Jingxin Li, Diana Zhou, Ming Yang, Melloni N Cook, Byron C Jones, Megan K Mulligan, Kristin M Hamre, Lu Lu
Alcohol abuse is a complex disorder, which is confounded by other factors, including stress. In the present study, we examined gene expression in the hippocampus of BXD recombinant inbred mice after exposure to ethanol (NOE), stress (RSS), and the combination of both (RSE). Mice were given an intraperitoneal (i.p.) injection of 1.8 g/kg ethanol or saline, and subsets of both groups were exposed to acute restraint stress for 15 min or controls. Gene expression in the hippocampus was examined using microarray analysis...
February 2017: Alcohol
https://www.readbyqxmd.com/read/27992444/evidence-of-recent-intricate-adaptation-in-human-populations
#8
Leeyoung Park
Recent human adaptations have shaped population differentiation in genomic regions containing putative functional variants, mostly located in predicted regulatory elements. However, their actual functionalities and the underlying mechanism of recent adaptation remain poorly understood. In the current study, regions of genes and repeats were investigated for functionality depending on the degree of population differentiation, FST or ΔDAF (a difference in derived allele frequency). The high FST in the 5´ or 3´ untranslated regions (UTRs), in particular, confirmed that population differences arose mainly from differences in regulation...
2016: PloS One
https://www.readbyqxmd.com/read/27922091/an-increased-duplication-of-zrs-region-that-caused-more-than-one-supernumerary-digits-preaxial-polydactyly-in-a-large-chinese-family
#9
Bin Wang, Yutao Diao, Qiji Liu, Hongqiang An, Ruiping Ma, Guosheng Jiang, Nannan Lai, Ziwei Li, Xiaoxiao Zhu, Lin Zhao, Qiang Guo, Zhen Zhang, Rong Sun, Xia Li
Preaxial polydactyly (PPD) is inherited in an autosomal dominant fashion and characterized by the presence of one or more supernumerary digits on the thumb side. It had been identified that point mutation or genomic duplications of the long-range limb-specific cis-regulator - zone of polarizing activity regulatory sequence (ZRS) cause PPD or other limb deformities such as syndactyly type IV (SD4) and Triphalangeal thumb-polysyndactyly syndrome (TPTPS). Most previously reported cases involved with no more than one extra finger; however, the role of the point mutation or genomic duplications of ZRS in the case of more than one redundant finger polydactyly remains unclear...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27918535/disease-variants-alter-transcription-factor-levels-and-methylation-of-their-binding-sites
#10
Marc Jan Bonder, René Luijk, Daria V Zhernakova, Matthijs Moed, Patrick Deelen, Martijn Vermaat, Maarten van Iterson, Freerk van Dijk, Michiel van Galen, Jan Bot, Roderick C Slieker, P Mila Jhamai, Michael Verbiest, H Eka D Suchiman, Marijn Verkerk, Ruud van der Breggen, Jeroen van Rooij, Nico Lakenberg, Wibowo Arindrarto, Szymon M Kielbasa, Iris Jonkers, Peter van 't Hof, Irene Nooren, Marian Beekman, Joris Deelen, Diana van Heemst, Alexandra Zhernakova, Ettje F Tigchelaar, Morris A Swertz, Albert Hofman, André G Uitterlinden, René Pool, Jenny van Dongen, Jouke J Hottenga, Coen D A Stehouwer, Carla J H van der Kallen, Casper G Schalkwijk, Leonard H van den Berg, Erik W van Zwet, Hailiang Mei, Yang Li, Mathieu Lemire, Thomas J Hudson, P Eline Slagboom, Cisca Wijmenga, Jan H Veldink, Marleen M J van Greevenbroek, Cornelia M van Duijn, Dorret I Boomsma, Aaron Isaacs, Rick Jansen, Joyce B J van Meurs, Peter A C 't Hoen, Lude Franke, Bastiaan T Heijmans
Most disease-associated genetic variants are noncoding, making it challenging to design experiments to understand their functional consequences. Identification of expression quantitative trait loci (eQTLs) has been a powerful approach to infer the downstream effects of disease-associated variants, but most of these variants remain unexplained. The analysis of DNA methylation, a key component of the epigenome, offers highly complementary data on the regulatory potential of genomic regions. Here we show that disease-associated variants have widespread effects on DNA methylation in trans that likely reflect differential occupancy of trans binding sites by cis-regulated transcription factors...
January 2017: Nature Genetics
https://www.readbyqxmd.com/read/27918533/identification-of-context-dependent-expression-quantitative-trait-loci-in-whole-blood
#11
Daria V Zhernakova, Patrick Deelen, Martijn Vermaat, Maarten van Iterson, Michiel van Galen, Wibowo Arindrarto, Peter van 't Hof, Hailiang Mei, Freerk van Dijk, Harm-Jan Westra, Marc Jan Bonder, Jeroen van Rooij, Marijn Verkerk, P Mila Jhamai, Matthijs Moed, Szymon M Kielbasa, Jan Bot, Irene Nooren, René Pool, Jenny van Dongen, Jouke J Hottenga, Coen D A Stehouwer, Carla J H van der Kallen, Casper G Schalkwijk, Alexandra Zhernakova, Yang Li, Ettje F Tigchelaar, Niek de Klein, Marian Beekman, Joris Deelen, Diana van Heemst, Leonard H van den Berg, Albert Hofman, André G Uitterlinden, Marleen M J van Greevenbroek, Jan H Veldink, Dorret I Boomsma, Cornelia M van Duijn, Cisca Wijmenga, P Eline Slagboom, Morris A Swertz, Aaron Isaacs, Joyce B J van Meurs, Rick Jansen, Bastiaan T Heijmans, Peter A C 't Hoen, Lude Franke
Genetic risk factors often localize to noncoding regions of the genome with unknown effects on disease etiology. Expression quantitative trait loci (eQTLs) help to explain the regulatory mechanisms underlying these genetic associations. Knowledge of the context that determines the nature and strength of eQTLs may help identify cell types relevant to pathophysiology and the regulatory networks underlying disease. Here we generated peripheral blood RNA-seq data from 2,116 unrelated individuals and systematically identified context-dependent eQTLs using a hypothesis-free strategy that does not require previous knowledge of the identity of the modifiers...
January 2017: Nature Genetics
https://www.readbyqxmd.com/read/27912247/molecular-evolution-of-insect-sociality-an-eco-evo-devo-perspective
#12
Amy L Toth, Sandra M Rehan
The evolution of eusociality is a perennial issue in evolutionary biology, and genomic advances have fueled steadily growing interest in the genetic changes underlying social evolution. Along with a recent flurry of research on comparative and evolutionary genomics in different eusocial insect groups (bees, ants, wasps, and termites), several mechanistic explanations have emerged to describe the molecular evolution of eusociality from solitary behavior. These include solitary physiological ground plans, genetic toolkits of deeply conserved genes, evolutionary changes in protein-coding genes, cis regulation, and the structure of gene networks, epigenetics, and novel genes...
January 31, 2017: Annual Review of Entomology
https://www.readbyqxmd.com/read/27875998/transcriptome-profiling-and-comparison-of-maize-ear-heterosis-during-the-spikelet-and-floret-differentiation-stages
#13
Xiaojiao Hu, Hongwu Wang, Xizhou Diao, Zhifang Liu, Kun Li, Yujin Wu, Qianjin Liang, Hui Wang, Changling Huang
BACKGROUND: Hybridization is a prominent process in the evolution of crop plants that can give rise to gene expression variation, phenotypic novelty and heterosis. Maize is the most successful crop in utilizing heterosis. The development of hybrid maize ears exhibits strong heterotic vigor and greatly affects maize yield. However, a comprehensive perspective on transcriptional variation and its correlation with heterosis during maize ear development is not available. RESULTS: Using RNA sequencing technology, we investigated the transcriptome profiles of maize ears in the spikelet and floret differentiation stages of hybrid ZD808 and its parents CL11 and NG5...
November 22, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27866169/a-new-mechanism-for-mendelian-dominance-in-regulatory-genetic-pathways-competitive-binding-by-transcription-factors
#14
Adam H Porter, Norman A Johnson, Alexander Y Tulchinsky
We report a new mechanism for allelic dominance in regulatory genetic interactions that we call binding dominance. We investigated a biophysical model of gene regulation, where the fractional occupancy of a transcription factor (TF) on the cis-regulated promoter site it binds to is determined by binding energy (-ΔG) and TF dosage. Transcription and gene expression proceed when the TF is bound to the promoter. In diploids, individuals may be heterozygous at the cis-site, at the TF's coding region, or at the TF's own promoter, which determines allele-specific dosage...
January 2017: Genetics
https://www.readbyqxmd.com/read/27831498/a-systematic-comparison-reveals-substantial-differences-in-chromosomal-versus-episomal-encoding-of-enhancer-activity
#15
Fumitaka Inoue, Martin Kircher, Beth Martin, Gregory M Cooper, Daniela M Witten, Michael T McManus, Nadav Ahituv, Jay Shendure
Candidate enhancers can be identified on the basis of chromatin modifications, the binding of chromatin modifiers and transcription factors and cofactors, or chromatin accessibility. However, validating such candidates as bona fide enhancers requires functional characterization, typically achieved through reporter assays that test whether a sequence can increase expression of a transcriptional reporter via a minimal promoter. A longstanding concern is that reporter assays are mainly implemented on episomes, which are thought to lack physiological chromatin...
January 2017: Genome Research
https://www.readbyqxmd.com/read/27729396/leaf-growth-response-to-mild-drought-natural-variation-in-arabidopsis-sheds-light-on-trait-architecture
#16
Pieter Clauw, Frederik Coppens, Arthur Korte, Dorota Herman, Bram Slabbinck, Stijn Dhondt, Twiggy Van Daele, Liesbeth De Milde, Mattias Vermeersch, Katrien Maleux, Steven Maere, Nathalie Gonzalez, Dirk Inzé
Plant growth and crop yield are negatively affected by a reduction in water availability. However, a clear understanding of how growth is regulated under nonlethal drought conditions is lacking. Recent advances in genomics, phenomics, and transcriptomics allow in-depth analysis of natural variation. In this study, we conducted a detailed screening of leaf growth responses to mild drought in a worldwide collection of Arabidopsis thaliana accessions. The genetic architecture of the growth responses upon mild drought was investigated by subjecting the different leaf growth phenotypes to genome-wide association mapping and by characterizing the transcriptome of young developing leaves...
October 2016: Plant Cell
https://www.readbyqxmd.com/read/27725110/expression-profile-of-long-noncoding-rnas-and-mrnas-in-peripheral-blood-mononuclear-cells-from-myasthenia-gravis-patients
#17
Fang Zhang, Guiyou Liu, Yali Bu, Xiaofeng Ma, Junwei Hao
For the epigenetic characterization of myasthenia gravis (MG), we determined whether long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) are expressed differentially in subjects with and without MG. Compared with healthy control subjects, the MG patients had 1561 upregulated lncRNAs, 1034 downregulated lncRNAs, 921 upregulated mRNAs, and 806 downregulated mRNAs (fold change>2.0). Several GO terms including nucleic acid transcription factor activity, inflammatory response, regulation of leukocyte activation, lymphocyte proliferation and regulation of B cell proliferation were enriched in gene lists, suggesting a potential correlation with MG...
October 15, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27685983/consensus-analysis-of-whole-transcriptome-profiles-from-two-breast-cancer-patient-cohorts-reveals-long-non-coding-rnas-associated-with-intrinsic-subtype-and-the-tumour-microenvironment
#18
James R Bradford, Angela Cox, Philip Bernard, Nicola J Camp
Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of cellular processes and diseases such as cancer; however, their functions remain poorly characterised. Several studies have demonstrated that lncRNAs are typically disease and tumour subtype specific, particularly in breast cancer where lncRNA expression alone is sufficient to discriminate samples based on hormone status and molecular intrinsic subtype. However, little attempt has been made to assess the reproducibility of lncRNA signatures across more than one dataset...
2016: PloS One
https://www.readbyqxmd.com/read/27670347/twister-ribozymes-as-highly-versatile-expression-platforms-for-artificial-riboswitches
#19
Michele Felletti, Julia Stifel, Lena A Wurmthaler, Sophie Geiger, Jörg S Hartig
The utilization of ribozyme-based synthetic switches in biotechnology has many advantages such as an increased robustness due to in cis regulation, small coding space and a high degree of modularity. The report of small endonucleolytic twister ribozymes provides new opportunities for the development of advanced tools for engineering synthetic genetic switches. Here we show that the twister ribozyme is distinguished as an outstandingly flexible expression platform, which in conjugation with three different aptamer domains, enables the construction of many different one- and two-input regulators of gene expression in both bacteria and yeast...
2016: Nature Communications
https://www.readbyqxmd.com/read/27646706/transcriptome-profiling-in-rat-inbred-strains-and-experimental-cross-reveals-discrepant-genetic-architecture-of-genome-wide-gene-expression
#20
Pamela J Kaisaki, Georg W Otto, Karène Argoud, Stephan C Collins, Robert H Wallis, Steven P Wilder, Anthony C Y Yau, Christophe Hue, Sophie Calderari, Marie-Thérèse Bihoreau, Jean-Baptiste Cazier, Richard Mott, Dominique Gauguier
To test the impact of genetic heterogeneity on cis- and trans-mediated mechanisms of gene expression regulation, we profiled the transcriptome of adipose tissue in 20 inbred congenic strains derived from diabetic Goto-Kakizaki (GK) rats and Brown-Norway (BN) controls, which contain well-defined blocks (1Mb-183Mb) of genetic polymorphisms, and in 123 genetically heterogeneous rats of an (GKxBN)F2 offspring. Within each congenic we identified 73 to 1,351 differentially expressed genes (DEG), only 7.7% of which mapped within the congenic blocks, and which may be regulated in cis The remainder localised outside the blocks, and therefore must be regulated in trans Most trans-regulated genes exhibited approximately two-fold expression changes, consistent with mono-allelic expression...
September 19, 2016: G3: Genes—Genomes—Genetics
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