The control of gene expression and cell proliferation by the epithelial apical junctional complex

2012 ◽  
Vol 53 ◽  
pp. 83-93 ◽  
Author(s):  
Domenica Spadaro ◽  
Rocio Tapia ◽  
Pamela Pulimeno ◽  
Sandra Citi
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Transcription Factors ◽  
Protein Complexes ◽  
Regulation Of Gene Expression ◽  
Small Gtpases ◽  
Junctional Complex ◽  
Nucleotide Exchange ◽  
Control Of Gene Expression ◽  
Apical Junctional Complex

The AJC (apical junctional complex) of vertebrate epithelial cells orchestrates cell–cell adhesion and tissue barrier function. In addition, it plays a pivotal role in signalling. Several protein components of the AJC, e.g. the cytoplasmic proteins β-catenin, p120-catenin and ZO (Zonula Occludens)-2, can shuttle to the nucleus, where they interact with transcription factors to regulate gene expression and cell proliferation. Other junctional proteins, e.g. angiomotin, α-catenin and cingulin, are believed to act by sequestering either transcription factors, such as YAP (Yes-associated protein), or regulators of small GTPases, such as GEF (guanine-nucleotide-exchange factor)-H1, at junctions. The signalling activities of AJC proteins are triggered by different extracellular and intracellular cues, including cell density, and physiological or pathological activation of developmentally regulated pathways, such as the Wnt pathway. The interplay between junctional protein complexes, the actin cytoskeleton and signalling pathways is of crucial importance in the regulation of gene expression and cell proliferation.

scholarly journals Chromatin-associated protein complexes link DNA base J and transcription termination in Leishmania

2020 ◽  
Author(s):  
Bryan C Jensen ◽  
Isabelle Q. Phan ◽  
Jacquelyn R. McDonald ◽  
Aakash Sur ◽  
Mark A. Gillespie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Protein Complexes ◽  
Transcription Termination ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Regulation Of Transcription ◽  
Control Of Gene Expression ◽  
Polycistronic Transcription ◽  
Post Transcriptional Regulation

AbstractUnlike most other eukaryotes, Leishmania and other trypanosomatid protozoa have largely eschewed transcriptional control of gene expression; relying instead on post-transcriptional regulation of mRNAs derived from polycistronic transcription units (PTUs). In these parasites, a novel modified nucleotide base (β-D-glucopyranosyloxymethyluracil) known as J plays a critical role in ensuring that transcription termination occurs only at the end of each PTU, rather than at the polyadenylation sites of individual genes. To further understand the biology of J-associated processes, we used tandem affinity purification (TAP-tagging) and mass spectrometry to reveal proteins that interact with the glucosyltransferase performing the final step in J synthesis. These studies identified four proteins reminiscent of subunits in the PTW/PP1 complex that controls transcription termination in higher eukaryotes. Moreover, bioinformatic analyses identified the DNA-binding subunit of Leishmania PTW/PP1 as a novel J-binding protein (JBP3). Down-regulation of JBP3 expression levels in Leishmania resulted in a substantial increase in transcriptional read-through at the 3’ end of most PTUs. Additional TAP-tagging experiments showed that JBP3 also associates with two other protein complexes. One consists of subunits with domains suggestive of a role in chromatin modification/remodeling; while the other contains subunits with similarity to those found in the PAF1 complex involved in regulation of transcription in other eukaryotes. Thus, trypanosomatids utilize protein complexes similar to those used to control transcription termination in other eukaryotes and JBP3 appears to function as a hub linking these modules to base J, thereby enabling the parasites’ unique reliance on polycistronic transcription and post-transcriptional regulation of gene expression.

scholarly journals Cell cycle regulated transcription: from yeast to cancer

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 877 ◽  
Author(s):  
Christopher J. McInerny
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Transcription Factors ◽  
Cell Division ◽  
Model Systems ◽  
Gene Products ◽  
Control Of Gene Expression ◽  
Forkhead Transcription Factors ◽  
Fundamental Process

Recent studies have revealed exciting new functions for forkhead transcription factors in cell proliferation and development. Cell proliferation is a fundamental process controlled by multiple overlapping mechanisms, and the control of gene expression plays a major role in the orderly and timely division of cells. This occurs through transcription factors regulating the expression of groups of genes at particular phases of the cell division cycle. In this way, the encoded gene products are present when they are required. This review outlines recent advances in our understanding of this process in yeast model systems and describes how this knowledge has informed analysis in more developmentally complex eukaryotes, particularly where it is relevant to human disease.

scholarly journals STAU2 protein level is controlled by caspases and the CHK1 pathway and regulates cell cycle progression in the non-transformed hTERT-RPE1 cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lionel Condé ◽  
Yulemi Gonzalez Quesada ◽  
Florence Bonnet-Magnaval ◽  
Rémy Beaujois ◽  
Luc DesGroseillers
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Steady State ◽  
Posttranscriptional Regulation ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Cycle Progression

AbstractBackgroundStaufen2 (STAU2) is an RNA binding protein involved in the posttranscriptional regulation of gene expression. In neurons, STAU2 is required to maintain the balance between differentiation and proliferation of neural stem cells through asymmetric cell division. However, the importance of controlling STAU2 expression for cell cycle progression is not clear in non-neuronal dividing cells. We recently showed that STAU2 transcription is inhibited in response to DNA-damage due to E2F1 displacement from theSTAU2gene promoter. We now study the regulation of STAU2 steady-state levels in unstressed cells and its consequence for cell proliferation.ResultsCRISPR/Cas9-mediated and RNAi-dependent STAU2 depletion in the non-transformed hTERT-RPE1 cells both facilitate cell proliferation suggesting that STAU2 expression influences pathway(s) linked to cell cycle controls. Such effects are not observed in the CRISPR STAU2-KO cancer HCT116 cells nor in the STAU2-RNAi-depleted HeLa cells. Interestingly, a physiological decrease in the steady-state level of STAU2 is controlled by caspases. This effect of peptidases is counterbalanced by the activity of the CHK1 pathway suggesting that STAU2 partial degradation/stabilization fines tune cell cycle progression in unstressed cells. A large-scale proteomic analysis using STAU2/biotinylase fusion protein identifies known STAU2 interactors involved in RNA translation, localization, splicing, or decay confirming the role of STAU2 in the posttranscriptional regulation of gene expression. In addition, several proteins found in the nucleolus, including proteins of the ribosome biogenesis pathway and of the DNA damage response, are found in close proximity to STAU2. Strikingly, many of these proteins are linked to the kinase CHK1 pathway, reinforcing the link between STAU2 functions and the CHK1 pathway. Indeed, inhibition of the CHK1 pathway for 4 h dissociates STAU2 from proteins involved in translation and RNA metabolism.ConclusionsThese results indicate that STAU2 is involved in pathway(s) that control(s) cell proliferation, likely via mechanisms of posttranscriptional regulation, ribonucleoprotein complex assembly, genome integrity and/or checkpoint controls. The mechanism by which STAU2 regulates cell growth likely involves caspases and the kinase CHK1 pathway.

scholarly journals Transcription Factors as the “Blitzkrieg” of Plant Defense: A Pragmatic View of Nitric Oxide’s Role in Gene Regulation

2021 ◽  
Vol 22 (2) ◽  
pp. 522
Author(s):  
Noreen Falak ◽  
Qari Muhammad Imran ◽  
Adil Hussain ◽  
Byung-Wook Yun
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Plant Defense ◽  
Systemic Acquired Resistance ◽  
Defense Mechanism ◽  
Regulation Of Gene Expression ◽  
Acquired Resistance ◽  
Biological Processes ◽  
Genetic Components ◽  
Transcriptional Changes

Plants are in continuous conflict with the environmental constraints and their sessile nature demands a fine-tuned, well-designed defense mechanism that can cope with a multitude of biotic and abiotic assaults. Therefore, plants have developed innate immunity, R-gene-mediated resistance, and systemic acquired resistance to ensure their survival. Transcription factors (TFs) are among the most important genetic components for the regulation of gene expression and several other biological processes. They bind to specific sequences in the DNA called transcription factor binding sites (TFBSs) that are present in the regulatory regions of genes. Depending on the environmental conditions, TFs can either enhance or suppress transcriptional processes. In the last couple of decades, nitric oxide (NO) emerged as a crucial molecule for signaling and regulating biological processes. Here, we have overviewed the plant defense system, the role of TFs in mediating the defense response, and that how NO can manipulate transcriptional changes including direct post-translational modifications of TFs. We also propose that NO might regulate gene expression by regulating the recruitment of RNA polymerase during transcription.

scholarly journals Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zi Wang ◽  
Pan Wang ◽  
Yanan Li ◽  
Hongling Peng ◽  
Yu Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Hematological Malignancies ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Hematologic Disorders ◽  
Cell Lineages ◽  
Stage Of Development ◽  
Transcription Complexes ◽  
Insight Into

AbstractHematopoiesis requires finely tuned regulation of gene expression at each stage of development. The regulation of gene transcription involves not only individual transcription factors (TFs) but also transcription complexes (TCs) composed of transcription factor(s) and multisubunit cofactors. In their normal compositions, TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis. The integration of posttranslational and conformational modifications in the chromatin landscape, nucleosomes, histones and interacting components via the cofactor–TF interplay is critical to optimal TF activity. Mutations or translocations of cofactor genes are expected to alter cofactor–TF interactions, which may be causative for the pathogenesis of various hematologic disorders. Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy. In this review, we summarize the current knowledge regarding the models and functions of cofactor–TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies. This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.

scholarly journals Minireview: Transcriptional Regulation in Development of Bone

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1012-1017 ◽  
Author(s):  
Tatsuya Kobayashi ◽  
Henry Kronenberg
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Bone Cells ◽  
Genetic Manipulation ◽  
Bone Development ◽  
Regulation Of Gene Expression ◽  
Bone Cell ◽  
Cellular Functions ◽  
Multiple Differentiation

Regulation of gene expression by transcription factors is one of the major mechanisms for controlling cellular functions. Recent advances in genetic manipulation of model animals has allowed the study of the roles of various genes and their products in physiological settings and has demonstrated the importance of specific transcription factors in bone development. Three lineages of bone cells, chondrocytes, osteoblasts, and osteoclasts, develop and differentiate according to their distinct developmental programs. These cells go through multiple differentiation stages, which are often regulated by specific transcription factors. In this minireview, we will discuss selected transcription factors that have been demonstrated to critically affect bone cell development. Further study of these molecules will lead to deeper understanding in mechanisms that govern development of bone.

scholarly journals Genome expression dynamics reveals parasitism regulatory landscape of the root-knot nematode Meloidogyne incognita and a promoter motif associated with effector genes

2021 ◽  
Author(s):  
Martine Da Rocha ◽  
Caroline Bournaud ◽  
Julie Dazeniere ◽  
Peter Thorpe ◽  
Clement Pellegrin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Meloidogyne Incognita ◽  
Life Stage ◽  
Regulation Of Gene Expression ◽  
Root Knot Nematode ◽  
Root Knot Nematodes ◽  
Control Of Gene Expression ◽  
Precise Control ◽  
Effector Genes ◽  
Spatio Temporal

Root-knot nematodes are the major contributor to the crop losses caused by nematodes. Root-knot nematodes secrete effectors into the plant, derived from two sets of pharyngeal gland cells, to manipulate host physiology and immunity. Successful completion of the life cycle, involving successive molts from egg to adult, covers morphologically and functionally distinct stages and will require precise control of gene expression, including effectors. The details of how root-knot nematodes regulate transcription remain sparse. Here, we report a life stage-specific transcriptome of Meloidogyne incognita. Combined with an available annotated genome, we explore the spatio-temporal regulation of gene expression. We reveal gene expression clusters and predicted functions that accompany the major developmental transitions. Focusing on effectors, we identify a putative cis-regulatory motif associated with expression in the dorsal glands: providing an insight into effector regulation. We combine the presence of this motif with several other criteria to predict a novel set of putative dorsal gland effectors. Finally, we show this motif, and thereby its utility, is broadly conserved across the Meloidogyne genus and termed it Mel-DOG. Taken together, we provide the first genome-wide analysis of spatio-temporal gene expression in a root-knot nematode, and identify a new set of candidate effector genes that will guide future functional analyses.

Principles of Molecular Biology

2013 ◽  
pp. 76-87
Author(s):  
Steven E. Hyman ◽  
Eric J. Nestler
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Molecular Biology ◽  
Cell Surface ◽  
Environmental Context ◽  
Molecular Processes ◽  
Control Of Gene Expression ◽  
Extracellular Signals ◽  
Gene Environment

This chapter provides an overview of the fundamental molecular processes by which information is encoded in the genome and how this information is expressed within an environmental context. We describe what genes are, how they function, and how their expression into RNA and protein is regulated by signals from outside the cell. Particular attention is given to a series of stimulus-regulated transcription factors, which play important roles in transducing information from the cell surface to the nucleus. Work in this area has shown that the control of gene expression by extracellular signals is a critical arena for gene–environment interactions that are highly relevant to psychiatry.

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