On the Nature and Specificity of DNA-Protein Interactions in the Regulation of Gene Expression

1987 ◽  
pp. 159-171
Author(s):  
Peter H. Hippel ◽  
Otto G. Berg
1994 ◽  
Vol 14 (10) ◽  
pp. 6635-6646
Author(s):  
J A Diehl ◽  
M Hannink

Protein-protein interactions between the CCAAT box enhancer-binding proteins (C/EBP) and the Rel family of transcription factors have been implicated in the regulation of cytokine gene expression. We have used sequence-specific DNA affinity chromatography to purify a complex from avian T cells that binds to a consensus C/EBP motif. Our results provide evidence that Rel-related proteins are components of the C/EBP-DNA complex as a result of protein-protein interactions with the C/EBP proteins. A polyclonal antiserum raised against the Rel homology domain of v-Rel and antisera raised against two human RelA-derived peptides specifically induced a supershift of the C/EBP-DNA complex in mobility shift assays using the affinity-purified C/EBP. In addition, several kappa B-binding proteins copurified with the avian C/EBP complex through two rounds of sequence-specific DNA affinity chromatography. The kappa B-binding proteins are distinct from the C/EBP proteins that directly contact DNA containing the C/EBP binding site. The identification of a protein complex that binds specifically to a consensus C/EBP site and contains both C/EBP and Rel family members suggests a novel mechanism for regulation of gene expression by Rel family proteins.


Author(s):  
Justine Y. Hansen ◽  
Ross D. Markello ◽  
Jacob W. Vogel ◽  
Jakob Seidlitz ◽  
Danilo Bzdok ◽  
...  

Regulation of gene expression drives protein interactions that govern synaptic wiring and neuronal activity. The resulting coordinated activity among neuronal populations supports complex psychological processes, yet how gene expression shapes cognition and emotion remains unknown. Here we directly bridge the microscale and macroscale by mapping gene expression patterns to functional activation patterns across the cortical sheet. Applying unsupervised learning to the Allen Human Brain Atlas and Neurosynth databases, we identify a ventromedial-dorsolateral gradient of gene assemblies that separate affective and cognitive domains. This topographic molecular-psychological signature reflects the hierarchical organization of the neocortex, including systematic variations in cell type, myeloarchitecture, laminar differentiation, and intrinsic network affiliation. In addition, this molecular-psychological signature is related to individual differences in cognitive performance, strengthens over neurodevelopment, and can be replicated in two independent repositories. Collectively, our results reveal spatially covarying transcriptomic and cognitive architectures, highlighting the influence that molecular mechanisms exert on psychological processes.


2015 ◽  
Vol 43 (3) ◽  
pp. 323-327 ◽  
Author(s):  
Swagat Ray ◽  
Pól Ó Catnaigh ◽  
Emma C. Anderson

Unr (upstream of N-ras) is a eukaryotic RNA-binding protein that has a number of roles in the post-transcriptional regulation of gene expression. Originally identified as an activator of internal initiation of picornavirus translation, it has since been shown to act as an activator and inhibitor of cellular translation and as a positive and negative regulator of mRNA stability, regulating cellular processes such as mitosis and apoptosis. The different post-transcriptional functions of Unr depend on the identity of its mRNA and protein partners and can vary with cell type and changing cellular conditions. Recent high-throughput analyses of RNA–protein interactions indicate that Unr binds to a large subset of cellular mRNAs, suggesting that Unr may play a wider role in translational responses to cellular signals than previously thought.


2005 ◽  
Vol 33 (6) ◽  
pp. 1405-1406 ◽  
Author(s):  
E. Kiss-Toth ◽  
D.H. Wyllie ◽  
K. Holland ◽  
L. Marsden ◽  
V. Jozsa ◽  
...  

Multiple cellular proteins have been identified as participating in Toll/interleukin-1 receptor-mediated inflammatory gene expression. The continuing isolation of novel components, based on sequence similarities, protein–protein interactions and protein purification, suggests that many elements of this signalling network remain to be identified. We report here the development of a high-throughput functional screening platform and its application for the identification of components of inflammatory signalling networks. Our results enable us to estimate that 100–150 gene products are involved in controlling the transcription of the human interleukin 8 gene. The approach, which is simple and robust, constitutes a general method for mapping signal transduction systems and for rapid isolation of a large number of signalling components based on the control of pathways leading to regulation of gene expression.


2020 ◽  
Author(s):  
Nicholas Treen ◽  
Shunsuke F. Shimobayashi ◽  
Jorine Eeftens ◽  
Clifford P. Brangwynne ◽  
Michael S. Levine

AbstractThere is emerging evidence for transcription condensates in the activation of gene expression1–3. However, there is considerably less information regarding transcriptional repression, despite its pervasive importance in regulating gene expression in development and disease. Here, we explore the role of liquid-liquid phase separation (LLPS) in the organization of the Groucho/TLE (Gro) family of transcriptional corepressors, which interact with a variety of sequence-specific repressors such as Hes/Hairy4. Gro-dependent repressors have been implicated in a variety of developmental processes, including segmentation of the Drosophila embryo and somitogenesis in vertebrates. These repressors bind to specific recognition sequences, but instead of interacting with coactivators (e.g., Mediator) they recruit Gro corepressors5. Gro contains a series of WD40 repeats that are thought to mediate oligomerization6. How putative Hes/Gro oligomers repress transcription has been the subject of numerous studies5, 6. Here we show that Hes/Gro complexes form discrete puncta within nuclei of living Ciona embryos. These puncta rapidly dissolve during the onset of mitosis and reappear in the ensuing cell cycle. Modified Hes/Gro complexes that are unable to bind DNA exhibit the properties of viscous liquid droplets, similar to those underlying the biogenesis of P-granules in C. elegans7 and nucleoli in Xenopus oocytes8. These observations provide vivid evidence for LLPS in the control of gene expression and suggest a simple physical exclusion mechanism for transcriptional repression. WD40 repeats have been implicated in a wide variety of cellular processes in addition to transcriptional repression9. We suggest that protein interactions using WD40 motifs might be a common feature of processes reliant on LLPS.


2014 ◽  
Vol 46 (13) ◽  
pp. 441-447 ◽  
Author(s):  
Hector Guillen-Ahlers ◽  
Michael R. Shortreed ◽  
Lloyd M. Smith ◽  
Michael Olivier

DNA-protein interactions are central to gene expression and chromatin regulation and have become one of the main focus areas of the ENCODE consortium. Advances in mass spectrometry and associated technologies have facilitated studies of these interactions, revealing many novel DNA-interacting proteins and histone posttranslational modifications. Proteins interacting at a single locus or at multiple loci have been targeted in these recent studies, each requiring a separate analytical strategy for isolation and analysis of DNA-protein interactions. The enrichment of target chromatin fractions occurs via a number of methods including immunoprecipitation, affinity purification, and hybridization, with the shared goal of using proteomics approaches as the final readout. The result of this is a number of exciting new tools, with distinct strengths and limitations that can enable highly robust and novel chromatin studies when applied appropriately. The present review compares and contrasts these methods to help the reader distinguish the advantages of each approach.


Author(s):  
Anthony Wong

Dr. Susanne Kohalmi is an Associate Professor in the Department of Biology at the Western University in London, Ontario. Her research is in molecular genetics, with focus on the regulation of gene expression and protein interactions. Currently her research is investigating the arogenate dehydratase enzyme family (ADTs) in the plant model organism Arabidopsis thaliana. In addition to research, she teaches undergraduate courses in genetics as well as supervising both undergraduate and graduate students. Anthony Wong, member of the Academic Affairs Committee at WURJHNS, interviewed Dr. Kohalmi to learn more about her research, her path to Western, and her advice to students.


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