scholarly journals Origin of the Functional Distinctiveness of NF-κB/p52

2021 ◽  
Vol 9 ◽  
Author(s):  
Gourisankar Ghosh ◽  
Vivien Ya-Fan Wang
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activation ◽  
Critical Factor ◽  
Dna Interactions ◽  
Response Elements ◽  
Sequence Variations ◽  
The Family ◽  
Transcription Regulators ◽  
And Function ◽  
Sequence Characteristics

The transcription regulators of the NF-κB family have emerged as a critical factor affecting the function of various adult tissues. The NF-κB family transcription factors are homo- and heterodimers made up of five monomers (p50, p52, RelA, cRel and RelB). The family is distinguished by sequence homology in their DNA binding and dimerization domains, which enables them to bind similar DNA response elements and participate in similar biological programs through transcriptional activation and repression of hundreds of genes. Even though the family members are closely related in terms of sequence and function, they all display distinct activities. In this review, we discuss the sequence characteristics, protein and DNA interactions, and pathogenic involvement of one member of family, NF-κB/p52, relative to that of other members. We pinpoint the small sequence variations within the conserved region that are mostly responsible for its distinct functional properties.

scholarly journals Negative regulation of nuclear factor-kappaB activation and function by glucocorticoids

2002 ◽  
Vol 28 (2) ◽  
pp. 69-78 ◽  
Author(s):  
WY Almawi ◽  
OK Melemedjian
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activation ◽  
Promoter Region ◽  
Nuclear Translocation ◽  
Nuclear Factor Kappab ◽  
Nuclear Factor ◽  
Creb Binding Protein ◽  
Transcriptional Initiation ◽  
Nf Kappab ◽  
And Function

Glucocorticoids (GCs) exert their anti-inflammatory and antiproliferative effects principally by inhibiting the expression of cytokines and adhesion molecules. Mechanistically, GCs diffuse through the cell membrane, and bind to their inactive cytosolic receptors (GRs), which then undergo conformational modifications that allow for their nuclear translocation. In the nucleus, activated GRs modulate transcriptional events by directly associating with DNA elements, compatible with the GCs response elements (GRE) motif, and located in variable copy numbers and at variable distances from the TATA box, in the promoter region of GC-responsive genes. In addition, activated GRs also acted by antagonizing the activity of transcription factors, in particular nuclear factor-kappaB (NF-kappaB), by direct and indirect mechanisms. GCs induced gene transcription and protein synthesis of the NF-kappaB inhibitor, IkappaB. Activated GR also antagonized NF-kappaB activity through protein-protein interaction involving direct complexing with, and inhibition of, NF-kappaB binding to DNA (Simple Model), or association with NF-kappaB bound to the kappaB DNA site (Composite Model). In addition, and according to the Transmodulation Model, GRE-bound GR may interact with and inhibit the activity of kappaB-bound NF-kappaB via a mechanism involving cross-talk between the two transcription factors. Lastly, GR may compete with NF-kappaB for nuclear coactivators, including CREB binding protein and p300, thereby reducing and inhibiting transcriptional activation by NF-kappaB. It should be noted that, in exerting its effect, activated GR did not affect the correct assembly of the pre-initiation (DAB) complex, but acted rather more proximally in inhibiting the correct assembly of transcription factors in the promoter region, and thus transcriptional initiation.

Regulating the development of pulmonary Group 2 innate lymphoid cells

2019 ◽  
Vol 400 (11) ◽  
pp. 1497-1507 ◽  
Author(s):  
Sofia Helfrich ◽  
Claudia U. Duerr
Keyword(s):  
Transcription Factors ◽  
Immune Responses ◽  
Morphological Changes ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
The Family ◽  
Intrinsic Regulation ◽  
Group 2 ◽  
And Function

Abstract Group 2 innate lymphoid cells (ILC2s) are members of the family of innate lymphoid cells and are innately committed to type 2 immune responses. In the lungs, ILC2s are the predominant population of innate lymphoid cells (ILCs) and their development is orchestrated by several different transcription factors ensuring lineage commitment by intrinsic regulation. ILC2s are present in the lungs from the foetal period onwards and are thus exposed to extrinsic regulation due to the airways’ continuous morphological changes upon birth. In this review, we will briefly summarise the dependence of ILC2s on transcription factors and discuss recently described characteristics and function of early life ILC2s in the lungs.

scholarly journals Distinguishable promoter elements are involved in transcriptional activation by E1a and cyclic AMP.

1989 ◽  
Vol 9 (10) ◽  
pp. 4390-4397 ◽  
Author(s):  
K A Lee ◽  
J S Fink ◽  
R H Goodman ◽  
M R Green
Keyword(s):  
Transcription Factors ◽  
Cyclic Amp ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Sequence Motif ◽  
Promoter Elements ◽  
Response Elements ◽  
Inducible Promoters ◽  
The Relationship ◽  
Cellular Transcription

The sequence motif CGTCA is critical for binding of a group of cellular transcription factors (ATF, CREB, E4F, and EivF) and for activation of certain E1a-inducible and cyclic AMP (cAMP)-inducible promoters. We have tested different promoter elements containing the CGTCA motif (referred to here as ATF-binding sites) for the ability to function as E1a or cAMP response elements. The adenovirus E4 promoter and the cellular vasoactive intestinal peptide (VIP) promoter responded differently to E1a and cAMP, demonstrating that the activating potential of ATF-binding sites within these promoters is not equivalent. While particular ATF-binding sites were sufficient for the activity of both the E4 (E1a inducibility) and VIP (cAMP inducibility) enhancers, these two enhancers had contrasting effects on E1a- and cAMP-inducible transcription. Thus, the relationship between E1a- and cAMP-inducible transcription is not simply explained by the action of these two inducers through the same promoter elements.

scholarly journals Genome-wide identification and characterization of Dof transcription factors in eggplant (Solanum melongena L.)

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4481 ◽  
Author(s):  
Qingzhen Wei ◽  
Wuhong Wang ◽  
Tianhua Hu ◽  
Haijiao Hu ◽  
Weihai Mao ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Expression Patterns ◽  
Solanum Melongena ◽  
Genome Database ◽  
Homologous Genes ◽  
Genome Wide ◽  
The Family ◽  
And Function

Eggplant (Solanum melongena L.) is an important vegetable cultivated in Asia, Africa and southern Europe and, following tomato and pepper, ranks as the third most important solanaceous vegetable crop. The Dof (DNA-binding with one finger) family is a group of plant-specific transcription factors that play important roles in plant growth, development, and response to biotic and abiotic stresses. The genes in the Dof family have been identified and analysed in many plant species, but the information remains lacking for eggplant. In the present study, we identified 29 SmeDof members from the eggplant genome database, which were classifed into nine subgroups. The phylogeny, gene structure, conserved motifs and homologous genes of SmeDof genes were comprehensively investigated. Subsequently, we analysed the expression patterns of SmeDof genes in six different eggplant subspecies. The results provide novel insights into the family of SmeDof genes and will promote the understanding of the structure and function of Dof genes in eggplant, and the role of Dof expression during stress.

Distinguishable promoter elements are involved in transcriptional activation by E1a and cyclic AMP

1989 ◽  
Vol 9 (10) ◽  
pp. 4390-4397
Author(s):  
K A Lee ◽  
J S Fink ◽  
R H Goodman ◽  
M R Green
Keyword(s):  
Transcription Factors ◽  
Cyclic Amp ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Sequence Motif ◽  
Promoter Elements ◽  
Response Elements ◽  
Inducible Promoters ◽  
The Relationship ◽  
Cellular Transcription

The sequence motif CGTCA is critical for binding of a group of cellular transcription factors (ATF, CREB, E4F, and EivF) and for activation of certain E1a-inducible and cyclic AMP (cAMP)-inducible promoters. We have tested different promoter elements containing the CGTCA motif (referred to here as ATF-binding sites) for the ability to function as E1a or cAMP response elements. The adenovirus E4 promoter and the cellular vasoactive intestinal peptide (VIP) promoter responded differently to E1a and cAMP, demonstrating that the activating potential of ATF-binding sites within these promoters is not equivalent. While particular ATF-binding sites were sufficient for the activity of both the E4 (E1a inducibility) and VIP (cAMP inducibility) enhancers, these two enhancers had contrasting effects on E1a- and cAMP-inducible transcription. Thus, the relationship between E1a- and cAMP-inducible transcription is not simply explained by the action of these two inducers through the same promoter elements.

scholarly journals Nfkb1Activation by the E26 Transformation-Specific Transcription Factors PU.1 and Spi-B Promotes Toll-Like Receptor-Mediated Splenic B Cell Proliferation

2015 ◽  
Vol 35 (9) ◽  
pp. 1619-1632 ◽  
Author(s):  
Stephen K. H. Li ◽  
Ali K. Abbas ◽  
Lauren A. Solomon ◽  
Gaëlle M. N. Groux ◽  
Rodney P. DeKoter
Keyword(s):  
Cell Proliferation ◽  
Transcription Factors ◽  
B Cells ◽  
B Cell ◽  
Transcriptional Activation ◽  
Chromatin Immunoprecipitation ◽  
Toll Like Receptor ◽  
Reporter Assays ◽  
Ets Family ◽  
And Function

Generation of antibodies against T-independent and T-dependent antigens requires Toll-like receptor (TLR) engagement on B cells for efficient responses. However, the regulation of TLR expression and responses in B cells is not well understood. PU.1 and Spi-B (encoded bySfpi1andSpib, respectively) are transcription factors of the E26 transformation-specific (ETS) family and are important for B cell development and function. It was found that B cells from mice knocked out for Spi-B and heterozygous for PU.1 (Sfpi1+/−Spib−/−[PUB] mice) proliferated poorly in response to TLR ligands compared to wild-type (WT) B cells. The NF-κB family member p50 (encoded byNfkb1) is required for lipopolysaccharide (LPS) responsiveness in mice.PUBB cells expressed reducedNfkb1mRNA transcripts and p50 protein. TheNfkb1promoter was regulated directly by PU.1 and Spi-B, as shown by reporter assays and chromatin immunoprecipitation analysis. Occupancy of theNfkb1promoter by PU.1 was reduced inPUBB cells compared to that in WT B cells. Finally, infection ofPUBB cells with a retroviral vector encoding p50 substantially restored proliferation in response to LPS. We conclude thatNfkb1transcriptional activation by PU.1 and Spi-B promotes TLR-mediated B cell proliferation.

Subnuclear compartmentalization of sequence-specific transcription factors and regulation of eukaryotic gene expression

2005 ◽  
Vol 83 (4) ◽  
pp. 535-547 ◽  
Author(s):  
Gareth N Corry ◽  
D Alan Underhill
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Current Knowledge ◽  
Nuclear Architecture ◽  
Subnuclear Localization ◽  
Modular Structures

To date, the majority of the research regarding eukaryotic transcription factors has focused on characterizing their function primarily through in vitro methods. These studies have revealed that transcription factors are essentially modular structures, containing separate regions that participate in such activities as DNA binding, protein–protein interaction, and transcriptional activation or repression. To fully comprehend the behavior of a given transcription factor, however, these domains must be analyzed in the context of the entire protein, and in certain cases the context of a multiprotein complex. Furthermore, it must be appreciated that transcription factors function in the nucleus, where they must contend with a variety of factors, including the nuclear architecture, chromatin domains, chromosome territories, and cell-cycle-associated processes. Recent examinations of transcription factors in the nucleus have clarified the behavior of these proteins in vivo and have increased our understanding of how gene expression is regulated in eukaryotes. Here, we review the current knowledge regarding sequence-specific transcription factor compartmentalization within the nucleus and discuss its impact on the regulation of such processes as activation or repression of gene expression and interaction with coregulatory factors.Key words: transcription, subnuclear localization, chromatin, gene expression, nuclear architecture.

scholarly journals NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells

2021 ◽  
Vol 22 (11) ◽  
pp. 5902
Author(s):  
Stefan Nagel ◽  
Claudia Pommerenke ◽  
Corinna Meyer ◽  
Hans G. Drexler
Keyword(s):  
Dendritic Cells ◽  
Transcription Factors ◽  
Cell Lines ◽  
Expression Profiling ◽  
Regulatory Network ◽  
Homeobox Gene ◽  
Leukemia Cell Line ◽  
Specific Gene ◽  
Rna Seq ◽  
And Function

Recently, we documented a hematopoietic NKL-code mapping physiological expression patterns of NKL homeobox genes in human myelopoiesis including monocytes and their derived dendritic cells (DCs). Here, we enlarge this map to include normal NKL homeobox gene expressions in progenitor-derived DCs. Analysis of public gene expression profiling and RNA-seq datasets containing plasmacytoid and conventional dendritic cells (pDC and cDC) demonstrated HHEX activity in both entities while cDCs additionally expressed VENTX. The consequent aim of our study was to examine regulation and function of VENTX in DCs. We compared profiling data of VENTX-positive cDC and monocytes with VENTX-negative pDC and common myeloid progenitor entities and revealed several differentially expressed genes encoding transcription factors and pathway components, representing potential VENTX regulators. Screening of RNA-seq data for 100 leukemia/lymphoma cell lines identified prominent VENTX expression in an acute myelomonocytic leukemia cell line, MUTZ-3 containing inv(3)(q21q26) and t(12;22)(p13;q11) and representing a model for DC differentiation studies. Furthermore, extended gene analyses indicated that MUTZ-3 is associated with the subtype cDC2. In addition to analysis of public chromatin immune-precipitation data, subsequent knockdown experiments and modulations of signaling pathways in MUTZ-3 and control cell lines confirmed identified candidate transcription factors CEBPB, ETV6, EVI1, GATA2, IRF2, MN1, SPIB, and SPI1 and the CSF-, NOTCH-, and TNFa-pathways as VENTX regulators. Live-cell imaging analyses of MUTZ-3 cells treated for VENTX knockdown excluded impacts on apoptosis or induced alteration of differentiation-associated cell morphology. In contrast, target gene analysis performed by expression profiling of knockdown-treated MUTZ-3 cells revealed VENTX-mediated activation of several cDC-specific genes including CSFR1, EGR2, and MIR10A and inhibition of pDC-specific genes like RUNX2. Taken together, we added NKL homeobox gene activities for progenitor-derived DCs to the NKL-code, showing that VENTX is expressed in cDCs but not in pDCs and forms part of a cDC-specific gene regulatory network operating in DC differentiation and function.

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