scholarly journals The transcription factor activity gradient (TAG) model: contemplating a contact-independent mechanism for enhancer–promoter communication

2021 ◽  
Author(s):  
Jonathan P. Karr ◽  
John J. Ferrie ◽  
Robert Tjian ◽  
Xavier Darzacq
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Regulatory Elements ◽  
Transcription Factor Activity ◽  
Factor Activity ◽  
New Model ◽  
Unresolved Question ◽  
Regulatory Information ◽  
Independent Mechanism ◽  
Coactivator P300

How distal cis-regulatory elements (e.g., enhancers) communicate with promoters remains an unresolved question of fundamental importance. Although transcription factors and cofactors are known to mediate this communication, the mechanism by which diffusible molecules relay regulatory information from one position to another along the chromosome is a biophysical puzzle—one that needs to be revisited in light of recent data that cannot easily fit into previous solutions. Here we propose a new model that diverges from the textbook enhancer–promoter looping paradigm and offer a synthesis of the literature to make a case for its plausibility, focusing on the coactivator p300.

scholarly journals Effect of aging on UVC-induced apoptosis of rat splenocytes.

2000 ◽  
Vol 47 (2) ◽  
pp. 339-347 ◽  
Author(s):  
E Radziszewska ◽  
K Piwocka ◽  
A Bielak-Zmijewska ◽  
J Skierski ◽  
E Sikora
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Morphological Changes ◽  
Transcription Factor Activity ◽  
Factor Activity ◽  
Dna Ladder ◽  
Young Rats ◽  
Bax Protein ◽  
Old Rats ◽  
Induced Apoptosis

UVC-induced apoptotic symptoms such as morphological changes, DNA fragmentation, Bcl-2 and Bax protein expression were examined in primary splenocyte cultures from young (3 months) and old (24 months) rats. The activities of AP-1 and CRE transcription factors in UVC-irradiated splenocytes were also assessed. At 24 h after UVC irradiation 40% of cells derived from young rats were found to be apoptotic, which was twice as much as in splenocytes from old rats. Apoptosis in cells from old rats did not give typical symptoms like a "DNA ladder" and Bcl-2 protein downregulation, in contrast to splenocytes from young rats. No AP-1 transcription factor activity was found in UVC-irradiated splenocytes from old animals and only a trace activity in splenocytes from young animals. This indicates that, UVC-induced apoptosis in rat splenocytes is practically AP-1 independent and that cells from old rats are less sensitive to UVC irradiation than splenocytes from young rats.

scholarly journals Detecting differential transcription factor activity from ATAC-seq data

2018 ◽  
Author(s):  
Ignacio J. Tripodi ◽  
Mary A. Allen ◽  
Robin D. Dowell
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Chromatin Accessibility ◽  
Open Chromatin ◽  
Nucleotide Polymorphisms ◽  
Transcription Factor Activity ◽  
Factor Activity ◽  
Genome Wide ◽  
Recognition Motifs ◽  
Differential Transcription

AbstractTranscription factors are managers of the cellular factory, and key components to many diseases. Many non-coding single nucleotide polymorphisms affect transcription factors, either by directly altering the protein or its functional activity at individual binding sites. Here we first briefly summarize high throughput approaches to studying transcription factor activity. We then demonstrate, using published chromatin accessibility data (specifically ATAC-seq), that the genome wide profile of TF recognition motifs relative to regions of open chromatin can determine the key transcription factor altered by a perturbation. Our method of determining which TF are altered by a perturbation is simple, quick to implement and can be used when biological samples are limited. In the future, we envision this method could be applied to determining which TFs show altered activity in response to a wide variety of drugs and diseases.

scholarly journals Transcription Factors of Lotus: Regulation of Isoflavonoid Biosynthesis Requires Coordinated Changes in Transcription Factor Activity

2012 ◽  
Vol 159 (2) ◽  
pp. 531-547 ◽  
Author(s):  
Dale Shelton ◽  
Maria Stranne ◽  
Lisbeth Mikkelsen ◽  
Nima Pakseresht ◽  
Tracey Welham ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Transcription Factor Activity ◽  
Factor Activity

scholarly journals Molecular mechanisms of transcription factor mediated cell reprogramming: conversion of liver to pancreas

2021 ◽  
Author(s):  
Sebastian L. Wild ◽  
David Tosh
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Cellular Reprogramming ◽  
Directed Differentiation ◽  
Transcription Factor Activity ◽  
Factor Activity ◽  
Cell Type ◽  
Β Cells ◽  
Master Regulator ◽  
Cellular Identity

Transdifferentiation is a type of cellular reprogramming involving the conversion of one differentiated cell type to another. This remarkable phenomenon holds enormous promise for the field of regenerative medicine. Over the last 20 years techniques used to reprogram cells to alternative identities have advanced dramatically. Cellular identity is determined by the transcriptional profile which comprises the subset of mRNAs, and therefore proteins, being expressed by a cell at a given point in time. A better understanding of the levers governing transcription factor activity benefits our ability to generate therapeutic cell types at will. One well-established example of transdifferentiation is the conversion of hepatocytes to pancreatic β-cells. This cell type conversion potentially represents a novel therapy in T1D treatment. The identification of key master regulator transcription factors (which distinguish one body part from another) during embryonic development has been central in developing transdifferentiation protocols. Pdx1 is one such example of a master regulator. Ectopic expression of vector-delivered transcription factors (particularly the triumvirate of Pdx1, Ngn3 and MafA) induces reprogramming through broad transcriptional remodelling. Increasingly, complimentary cell culture techniques, which recapitulate the developmental microenvironment, are employed to coax cells to adopt new identities by indirectly regulating transcription factor activity via intracellular signalling pathways. Both transcription factor-based reprogramming and directed differentiation approaches ultimately exploit transcription factors to influence cellular identity. Here, we explore the evolution of reprogramming and directed differentiation approaches within the context of hepatocyte to β-cell transdifferentiation focussing on how the introduction of new techniques has improved our ability to generate β-cells.

scholarly journals Expression analysis of transcription factors in sugarcane during cold stress

2023 ◽  
Vol 83 ◽  
Author(s):  
S. U. Rehman ◽  
K. Muhammad ◽  
E. Novaes ◽  
Y. Que ◽  
A. Din ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Rna Polymerase ◽  
Cold Stress ◽  
Rna Polymerase Ii ◽  
Rna Polymerase Iii ◽  
Regulatory Region ◽  
Transcription Factor Activity ◽  
Factor Activity ◽  
Upregulated Genes

Abstract Transcription factors (TF) are a wide class of genes in plants, and these can regulate the expression of other genes in response to various environmental stresses (biotic and abiotic). In the current study, transcription factor activity in sugarcane was examined during cold stress. Initially, RNA transcript reads of two sugarcane cultivars (ROC22 and GT08-1108) under cold stress were downloaded from SRA NCBI database. The reads were aligned into a reference genome and the differential expression analyses were performed with the R/Bioconductor edgeR package. Based on our analyses in the ROC22 cultivar, 963 TF genes were significantly upregulated under cold stress among a total of 5649 upregulated genes, while 293 TF genes were downregulated among a total of 3,289 downregulated genes. In the GT08-1108 cultivar, 974 TF genes were identified among 5,649 upregulated genes and 283 TF genes were found among 3,289 downregulated genes. Most transcription factors were annotated with GO categories related to protein binding, transcription factor binding, DNA-sequence-specific binding, transcription factor complex, transcription factor activity in RNA polymerase II, the activity of nucleic acid binding transcription factor, transcription corepressor activity, sequence-specific regulatory region, the activity of transcription factor of RNA polymerase II, transcription factor cofactor activity, transcription factor activity from plastid promoter, transcription factor activity from RNA polymerase I promoter, polymerase II and RNA polymerase III. The findings of above results will help to identify differentially expressed transcription factors during cold stress. It also provides a comprehensive analysis of the regulation of the transcription activity of many genes. Therefore, this study provides the molecular basis for improving cold tolerance in sugarcane and other economically important grasses.

scholarly journals Transcription factor activity and nucleosome organisation in mitosis

2018 ◽  
Author(s):  
Nicola Festuccia ◽  
Nick Owens ◽  
Thaleia Papadopoulou ◽  
Inma Gonzalez ◽  
Alexandra Tachtsidi ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Embryonic Stem ◽  
Transcription Factor Activity ◽  
Factor Activity ◽  
Mitotic Chromosomes ◽  
Daughter Cells ◽  
Regulatory Information ◽  
Chromosomal Association ◽  
Transient Interactions ◽  
Gene Regulatory

Mitotic bookmarking transcription factors (BFs) maintain the capacity to bind to their targets during mitosis, despite major rearrangements of the chromatin. While they were thought to propagate gene regulatory information through mitosis by statically occupying their DNA targets, it has recently become clear that BFs are highly dynamic in mitotic cells. This represents both a technical and a conceptual challenge to study and understand the function of BFs: first, formaldehyde has been suggested to be unable to efficiently capture these transient interactions, leading to profound contradictions in the literature; second, if BFs are not permanently bound to their targets during mitosis, it becomes unclear how they convey regulatory information to daughter cells. Here, comparing formaldehyde to alternative fixatives we clarify the nature of the chromosomal association of previously proposed BFs in embryonic stem cells: while Esrrb can be considered as a canonical BF that binds at selected regulatory regions in mitosis, Sox2 and Oct4 establish DNA sequence independent interactions with the mitotic chromosomes, either throughout the chromosomal arms (Sox2) or at pericentromeric regions (Oct4). Moreover, we show that ordered nucleosomal arrays are retained during mitosis at Esrrb book-marked sites, whereas regions losing transcription factor binding display a profound loss of order. By maintaining nucleosome positioning during mitosis, Esrrb might ensure the rapid post-mitotic re-establishment of functional regulatory complexes at selected enhancers and promoters. Our results provide a mechanistic framework that reconciles dynamic mitotic binding with the transmission of gene regulatory information across cell division.

scholarly journals Genome-Wide Signatures of Transcription Factor Activity: Connecting Transcription Factors, Disease, and Small Molecules

2013 ◽  
Vol 9 (9) ◽  
pp. e1003198 ◽  
Author(s):  
Jing Chen ◽  
Zhen Hu ◽  
Mukta Phatak ◽  
John Reichard ◽  
Johannes M. Freudenberg ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Small Molecules ◽  
Transcription Factor Activity ◽  
Factor Activity ◽  
Genome Wide

scholarly journals Dynamic transcription factor activity and networks during ErbB2 breast oncogenesis and targeted therapy

2014 ◽  
Vol 6 (12) ◽  
pp. 1170-1182 ◽  
Author(s):  
M. S. Weiss ◽  
B. Peñalver Bernabé ◽  
S. Shin ◽  
S. Asztalos ◽  
S. J. Dubbury ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Targeted Therapy ◽  
Real Time ◽  
Cell Fate ◽  
3D Culture ◽  
Computational Approach ◽  
Transcription Factor Activity ◽  
Factor Activity ◽  
Real Time Identification

A novel experimental and computational approach for real time identification of transcription factors regulating cell fate throughout differentiation in 3D culture.

LMWF5A suppresses cytokine release by modulating select inflammatory transcription factor activity in stimulated PBMC

2020 ◽  
Author(s):  
Gregory Thomas ◽  
Elizabeth Frederick ◽  
Lisa Thompson ◽  
Raphael Bar-Or ◽  
Yetti Mulugeta ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Dna Binding ◽  
Inflammatory Cytokine ◽  
Transcription Factor Activity ◽  
Cytokine Release ◽  
Factor Activity ◽  
Gene Enrichment ◽  
Reporter Assays

Abstract Background Dysregulation of transcription and cytokine expression has been implicated in the pathogenesis of a variety inflammatory diseases. The resulting imbalance between inflammatory and resolving transcriptional programs can cause an overabundance of pro-inflammatory, classically activated macrophage type 1 (M1) and/or helper T cell type 1 (Th1) products, such as IFNγ, TNFα, IL1-β, and IL12, that prevent immune switching to resolution and healing. The low molecular weight fraction of human serum albumin (LMWF5A) is novel biologic drug that is currently under clinical investigation for the treatment of osteoarthritis and the hyper-inflammatory response associated with COVID-19. This study aims to elucidate transcriptional mechanisms of action involved with the ability of LMWF5A to reduce pro-inflammatory cytokine release. Methods ELISA arrays were used to identify cytokines and chemokines influenced by LMWF5A treatment of LPS-stimulated peripheral blood mononuclear cells (PBMC). The resulting profiles were analyzed by gene enrichment to gain mechanistic insight into the biologic processes and transcription factors (TFs) underlying the identified differentially expressed cytokines. DNA-binding ELISAs, luciferase reporter assays, and TNFα or IL-1β relative potency were then employed to confirm the involvement of enriched pathways and TFs.Results LMWF5A was found to significantly inhibit a distinct set of pro-inflammatory cytokines (TNFα, IL-1β, IL-12, CXCL9, CXCL10, and CXCL11) associated with pro-inflammatory M1/Th1 immune profiles. Gene enrichment analysis also suggests these cytokines are, in part, regulated by NF-κB and STAT transcription factors. Data from DNA-binding and reporter assays support this with LMWF5A inhibition of STAT1α DNA-binding activity as well as a reduction in overall NF-κB-driven luciferase expression. Experiments using antagonists specific for the immunomodulatory and NF-κB/STAT-repressing transcription factors, peroxisome proliferator-activated receptor (PPAR)γ and aryl hydrocarbon receptor (AhR), indicate these pathways are involved in the LMWF5A mechanism of action by reducing LMWF5A drug potency as measured by TNFα and IL-1β release. Conclusion In this report, we provide evidence that LMWF5A reduces pro-inflammatory cytokine release by activating the immunoregulatory transcription factors PPARγ and AhR. In addition, our data indicate that LMWF5A suppresses NF-κB and STAT1α pro-inflammatory pathways. This suggests that LMWF5A act through these mechanisms to decrease pro-inflammatory transcription factor activity and subsequent inflammatory cytokine production.

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