The Experts below are selected from a list of 380997 Experts worldwide ranked by ideXlab platform
Chunbo Lou - One of the best experts on this subject based on the ideXlab platform.
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engineering the ultrasensitive Transcription Factors by fusing a modular oligomerization domain
ACS Synthetic Biology, 2018Co-Authors: Junran Hou, Weiqian Zeng, Yeqing Zong, Zehua Chen, Chensi Miao, Baojun Wang, Chunbo LouAbstract:The dimerization and high-order oligomerization of Transcription Factors has endowed them with cooperative regulatory capabilities that play important roles in many cellular functions. However, such advanced regulatory capabilities have not been fully exploited in synthetic biology and genetic engineering. Here, we engineered a C-terminally fused oligomerization domain to improve the cooperativity of Transcription Factors. First, we found that two of three designed oligomerization domains significantly increased the cooperativity and ultrasensitivity of a Transcription factor for the regulated promoter. Then, seven additional Transcription Factors were used to assess the modularity of the oligomerization domains, and their ultrasensitivity was generally improved, as assessed by their Hill coefficients. Moreover, we also demonstrated that the allosteric capability of the ligand-responsive domain remained intact when fusing with the designed oligomerization domain. As an example application, we showed that ...
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Engineering the Ultrasensitive Transcription Factors by Fusing a Modular Oligomerization Domain
2018Co-Authors: Junran Hou, Weiqian Zeng, Yeqing Zong, Zehua Chen, Chensi Miao, Baojun Wang, Chunbo LouAbstract:The dimerization and high-order oligomerization of Transcription Factors has endowed them with cooperative regulatory capabilities that play important roles in many cellular functions. However, such advanced regulatory capabilities have not been fully exploited in synthetic biology and genetic engineering. Here, we engineered a C-terminally fused oligomerization domain to improve the cooperativity of Transcription Factors. First, we found that two of three designed oligomerization domains significantly increased the cooperativity and ultrasensitivity of a Transcription factor for the regulated promoter. Then, seven additional Transcription Factors were used to assess the modularity of the oligomerization domains, and their ultrasensitivity was generally improved, as assessed by their Hill coefficients. Moreover, we also demonstrated that the allosteric capability of the ligand-responsive domain remained intact when fusing with the designed oligomerization domain. As an example application, we showed that the engineered ultrasensitive Transcription factor could be used to significantly improve the performance of a “stripe-forming” gene circuit. We envision that the oligomerization modules engineered in this study could act as a powerful tool to rapidly tune the underlying response profiles of synthetic gene circuits and metabolic pathway controllers
S. L. Peng - One of the best experts on this subject based on the ideXlab platform.
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forkhead Transcription Factors in chronic inflammation
The International Journal of Biochemistry & Cell Biology, 2010Co-Authors: S. L. PengAbstract:Forkhead (Fox) Transcription Factors have been increasingly recognized to play key roles in immune homeostasis, especially Foxp3 for its role in the development and function of regulatory T cells, and Foxo family members for their regulatory role in T and B lymphocytes as well as other leukocytes. Although these Transcription Factors positively regulate the expression of multiple target genes, a unique functional attribute of these genes is the maintenance of leukocyte homeostasis, such as the preservation of the naive or quiescent T cell state and prevention of autoimmunity. As a result, many chronic inflammatory processes appear to reflect a relative loss of activity of one of these Transcription Factors, raising the possibility that therapeutic approaches which confer gain-of-function Fox activity may be beneficial. On the other hand, however, some of the Fox family members also appear to promote and/or maintain chronic inflammation by preserving inflammatory leukocyte survival and/or otherwise promoting the expression of inflammatory target genes, at least in some cell types such as neutrophils. Therefore, although the role of Fox in inflammatory disorders remains complex and incompletely understood, the continued study of these Factors provides new insight into the initiation, maintenance, and propagation of inflammation.
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Forkhead Transcription Factors in immunology
Cellular and Molecular Life Sciences CMLS, 2005Co-Authors: H. Jonsson, S. L. PengAbstract:The forkhead (Fox) gene family comprises a diverse group of ‘winged-helix’ Transcription Factors that play important roles in development, metabolism, cancer and aging. Recently, several forkhead genes have been demonstrated to play critical roles in lymphocyte development and effector function, including Foxp3 in the development of regulatory T cells, Foxj1 and Foxo3a in the regulation of CD4^+ T cell tolerance, and Foxn1 in thymic development. Roles for other forkhead genes have also been proposed, including Foxp1 in macrophage differentiation, Foxq1 in natural killer cell effector function and Foxd2 in T cell activation. Thus, forkhead genes promise insight into the mechanisms of immunoregulation in several immune cell lineages, and their dysregulation likely contributes to the pathogenesis of several immunological disorders, suggesting that their study will lead to the development of novel therapeutic agents.
Kazuko Yamaguchishinozaki - One of the best experts on this subject based on the ideXlab platform.
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nac Transcription Factors in plant abiotic stress responses
Biochimica et Biophysica Acta, 2012Co-Authors: Kazuo Nakashima, Junya Mizoi, Kazuo Shinozaki, Hironori Takasaki, Kazuko YamaguchishinozakiAbstract:Abiotic stresses such as drought and high salinity adversely affect the growth and productivity of plants, including crops. The development of stress-tolerant crops will be greatly advantageous for modern agriculture in areas that are prone to such stresses. In recent years, several advances have been made towards identifying potential stress related genes which are capable of increasing the tolerance of plants to abiotic stress. NAC proteins are plant-specific Transcription Factors and more than 100 NAC genes have been identified in Arabidopsis and rice to date. Phylogenetic analyses indicate that the six major groups were already established at least in an ancient moss lineage. NAC Transcription Factors have a variety of important functions not only in plant development but also in abiotic stress responses. Stress-inducible NAC genes have been shown to be involved in abiotic stress tolerance. Transgenic Arabidopsis and rice plants overexpressing stress-responsive NAC (SNAC) genes have exhibited improved drought tolerance. These studies indicate that SNAC Factors have important roles for the control of abiotic stress tolerance and that their overexpression can improve stress tolerance via biotechnological approaches. Although these Transcription Factors can bind to the same core NAC recognition sequence, recent studies have demonstrated that the effects of NAC Factors for growth are different. Moreover, the NAC proteins are capable of functioning as homo- or hetero-dimer forms. Thus, SNAC Factors can be useful for improving stress tolerance in transgenic plants, although the mechanism for mediating the stress tolerance of these homologous Factors is complex in plants. Recent studies also suggest that crosstalk may exist between stress responses and plant growth. This article is part of a Special Issue entitled: Plant gene regulation in response to abiotic stress.
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ap2 erf family Transcription Factors in plant abiotic stress responses
Biochimica et Biophysica Acta, 2012Co-Authors: Junya Mizoi, Kazuo Shinozaki, Kazuko YamaguchishinozakiAbstract:In terrestrial environments, temperature and water conditions are highly variable, and extreme temperatures and water conditions affect the survival, growth and reproduction of plants. To protect cells and sustain growth under such conditions of abiotic stress, plants respond to unfavourable changes in their environments in developmental, physiological and biochemical ways. These responses require expression of stress-responsive genes, which are regulated by a network of Transcription Factors. The AP2/ERF family is a large family of plant-specific Transcription Factors that share a well-conserved DNA-binding domain. This Transcription factor family includes DRE-binding proteins (DREBs), which activate the expression of abiotic stress-responsive genes via specific binding to the dehydration-responsive element/C-repeat (DRE/CRT) cis-acting element in their promoters. In this review, we discuss the functions of the AP2/ERF-type Transcription Factors in plant abiotic stress responses, with special emphasis on the regulations and functions of two major types of DREBs, DREB1/CBF and DREB2. In addition, we summarise the involvement of other AP2/ERF-type Transcription Factors in abiotic stress responses, which has recently become clear. This article is part of a Special Issue entitled: Plant gene regulation in response to abiotic stress.
Dana T. Graves - One of the best experts on this subject based on the ideXlab platform.
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Role of Forkhead Transcription Factors in Diabetes-Induced Oxidative Stress
Experimental diabetes research, 2012Co-Authors: Bhaskar Ponugoti, Guangyu Dong, Dana T. GravesAbstract:Diabetes is a chronic metabolic disorder, characterized by hyperglycemia resulting from insulin deficiency and/or insulin resistance. Recent evidence suggests that high levels of reactive oxygen species (ROS) and subsequent oxidative stress are key contributors in the development of diabetic complications. The FOXO family of forkhead Transcription Factors including FOXO1, FOXO3, FOXO4, and FOXO6 play important roles in the regulation of many cellular and biological processes and are critical regulators of cellular oxidative stress response pathways. FOXO1 Transcription Factors can affect a number of different tissues including liver, retina, bone, and cell types ranging from hepatocytes to microvascular endothelial cells and pericytes to osteoblasts. They are induced by oxidative stress and contribute to ROS-induced cell damage and apoptosis. In this paper, we discuss the role of FOXO Transcription Factors in mediating oxidative stress-induced cellular response.
Kenneth S Zaret - One of the best experts on this subject based on the ideXlab platform.
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cell fate control by pioneer Transcription Factors
Development, 2016Co-Authors: Makiko Iwafuchidoi, Kenneth S ZaretAbstract:Distinct combinations of Transcription Factors are necessary to elicit cell fate changes in embryonic development. Yet within each group of fate-changing Transcription Factors, a subset called ‘pioneer Factors’ are dominant in their ability to engage silent, unmarked chromatin and initiate the recruitment of other Factors, thereby imparting new function to regulatory DNA sequences. Recent studies have shown that pioneer Factors are also crucial for cellular reprogramming and that they are implicated in the marked changes in gene regulatory networks that occur in various cancers. Here, we provide an overview of the contexts in which pioneer Factors function, how they can target silent genes, and their limitations at regions of heterochromatin. Understanding how pioneer Factors regulate gene expression greatly enhances our understanding of how specific developmental lineages are established as well as how cell fates can be manipulated.
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pioneer Transcription Factors chromatin dynamics and cell fate control
Current Opinion in Genetics & Development, 2016Co-Authors: Kenneth S Zaret, Susan E MangoAbstract:Among the diverse Transcription Factors that are necessary to elicit changes in cell fate, both in embryonic development and in cellular reprogramming, a subset of Factors are capable of binding to their target sequences on nucleosomal DNA and initiating regulatory events in silent chromatin. Such 'pioneer Transcription Factors' initiate cooperative interactions with other regulatory proteins to elicit changes in local chromatin structure. As a consequence of pioneer factor binding, the local chromatin can either become open and competent for activation, closed and repressed, or Transcriptionally active. Understanding how pioneer Factors initiate chromatin dynamics and how such can be blocked at heterochromatic sites provides insights into controlling cell fate transitions at will.
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pioneer Transcription Factors establishing competence for gene expression
Genes & Development, 2011Co-Authors: Kenneth S Zaret, Jason S. CarrollAbstract:Transcription Factors are adaptor molecules that detect regulatory sequences in the DNA and target the assembly of protein complexes that control gene expression. Yet much of the DNA in the eukaryotic cell is in nucleosomes and thereby occluded by histones, and can be further occluded by higher-order chromatin structures and repressor complexes. Indeed, genome-wide location analyses have revealed that, for all Transcription Factors tested, the vast majority of potential DNA-binding sites are unoccupied, demonstrating the inaccessibility of most of the nuclear DNA. This raises the question of how target sites at silent genes become bound de novo by Transcription Factors, thereby initiating regulatory events in chromatin. Binding cooperativity can be sufficient for many kinds of Factors to simultaneously engage a target site in chromatin and activate gene expression. However, in cases in which the binding of a series of Factors is sequential in time and thus not initially cooperative, special "pioneer Transcription Factors" can be the first to engage target sites in chromatin. Such initial binding can passively enhance Transcription by reducing the number of additional Factors that are needed to bind the DNA, culminating in activation. In addition, pioneer factor binding can actively open up the local chromatin and directly make it competent for other Factors to bind. Passive and active roles for the pioneer factor FoxA occur in embryonic development, steroid hormone induction, and human cancers. Herein we review the field and describe how pioneer Factors may enable cellular reprogramming.
