scholarly journals Class I TCP transcription factors regulate trichome branching and cuticle development in Arabidopsis

2020 ◽  
Vol 71 (18) ◽  
pp. 5438-5453
Author(s):  
Alejandra Camoirano ◽  
Agustín L Arce ◽  
Federico D Ariel ◽  
Antonela L Alem ◽  
Daniel H Gonzalez ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Regulatory Network ◽  
Class I ◽  
Branch Number ◽  
Plant Organ ◽  
Cuticle Formation ◽  
Cuticle Development ◽  
Different Levels

Abstract Trichomes and the cuticle are two specialized structures of the aerial epidermis that are important for plant organ development and interaction with the environment. In this study, we report that Arabidopsis thaliana plants affected in the function of the class I TEOSINTE BRANCHED 1, CYCLOIDEA, PCF (TCP) transcription factors TCP14 and TCP15 show overbranched trichomes in leaves and stems and increased cuticle permeability. We found that TCP15 regulates the expression of MYB106, a MIXTA-like transcription factor involved in epidermal cell and cuticle development, and overexpression of MYB106 in a tcp14 tcp15 mutant reduces trichome branch number. TCP14 and TCP15 are also required for the expression of the cuticle biosynthesis genes CYP86A4, GPAT6, and CUS2, and of SHN1 and SHN2, two AP2/EREBP transcription factors required for cutin and wax biosynthesis. SHN1 and CUS2 are also targets of TCP15, indicating that class I TCPs influence cuticle formation acting at different levels, through the regulation of MIXTA-like and SHN transcription factors and of cuticle biosynthesis genes. Our study indicates that class I TCPs are coordinators of the regulatory network involved in trichome and cuticle development.

scholarly journals Regulatory Network Analysis in Estradiol-Treated Human Endothelial Cells

2021 ◽  
Vol 22 (15) ◽  
pp. 8193
Author(s):  
Daniel Pérez-Cremades ◽  
Ana B. Paes ◽  
Xavier Vidal-Gómez ◽  
Ana Mompeón ◽  
Carlos Hermenegildo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Regulatory Network ◽  
Mirna Target ◽  
Target Genes ◽  
Functional Characterization ◽  
Human Endothelial Cells ◽  
Mrna Targets ◽  
Canonical Pathways

Background/Aims: Estrogen has been reported to have beneficial effects on vascular biology through direct actions on endothelium. Together with transcription factors, miRNAs are the major drivers of gene expression and signaling networks. The objective of this study was to identify a comprehensive regulatory network (miRNA-transcription factor-downstream genes) that controls the transcriptomic changes observed in endothelial cells exposed to estradiol. Methods: miRNA/mRNA interactions were assembled using our previous microarray data of human umbilical vein endothelial cells (HUVEC) treated with 17β-estradiol (E2) (1 nmol/L, 24 h). miRNA–mRNA pairings and their associated canonical pathways were determined using Ingenuity Pathway Analysis software. Transcription factors were identified among the miRNA-regulated genes. Transcription factor downstream target genes were predicted by consensus transcription factor binding sites in the promoter region of E2-regulated genes by using JASPAR and TRANSFAC tools in Enrichr software. Results: miRNA–target pairings were filtered by using differentially expressed miRNAs and mRNAs characterized by a regulatory relationship according to miRNA target prediction databases. The analysis identified 588 miRNA–target interactions between 102 miRNAs and 588 targets. Specifically, 63 upregulated miRNAs interacted with 295 downregulated targets, while 39 downregulated miRNAs were paired with 293 upregulated mRNA targets. Functional characterization of miRNA/mRNA association analysis highlighted hypoxia signaling, integrin, ephrin receptor signaling and regulation of actin-based motility by Rho among the canonical pathways regulated by E2 in HUVEC. Transcription factors and downstream genes analysis revealed eight networks, including those mediated by JUN and REPIN1, which are associated with cadherin binding and cell adhesion molecule binding pathways. Conclusion: This study identifies regulatory networks obtained by integrative microarray analysis and provides additional insights into the way estradiol could regulate endothelial function in human endothelial cells.

scholarly journals Single cell characterization of B-lymphoid differentiation and leukemic cell states during chemotherapy in ETV6-RUNX1-positive pediatric leukemia identifies drug-targetable transcription factor activities

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Juha Mehtonen ◽  
Susanna Teppo ◽  
Mari Lahnalampi ◽  
Aleksi Kokko ◽  
Riina Kaukonen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Regulatory Network ◽  
Leukemic Cell ◽  
Immune Microenvironment ◽  
Ets Transcription Factors ◽  
Lineage Differentiation ◽  
B Lineage

Abstract Background Tight regulatory loops orchestrate commitment to B cell fate within bone marrow. Genetic lesions in this gene regulatory network underlie the emergence of the most common childhood cancer, acute lymphoblastic leukemia (ALL). The initial genetic hits, including the common translocation that fuses ETV6 and RUNX1 genes, lead to arrested cell differentiation. Here, we aimed to characterize transcription factor activities along the B-lineage differentiation trajectory as a reference to characterize the aberrant cell states present in leukemic bone marrow, and to identify those transcription factors that maintain cancer-specific cell states for more precise therapeutic intervention. Methods We compared normal B-lineage differentiation and in vivo leukemic cell states using single cell RNA-sequencing (scRNA-seq) and several complementary genomics profiles. Based on statistical tools for scRNA-seq, we benchmarked a workflow to resolve transcription factor activities and gene expression distribution changes in healthy bone marrow lymphoid cell states. We compared these to ALL bone marrow at diagnosis and in vivo during chemotherapy, focusing on leukemias carrying the ETV6-RUNX1 fusion. Results We show that lymphoid cell transcription factor activities uncovered from bone marrow scRNA-seq have high correspondence with independent ATAC- and ChIP-seq data. Using this comprehensive reference for regulatory factors coordinating B-lineage differentiation, our analysis of ETV6-RUNX1-positive ALL cases revealed elevated activity of multiple ETS-transcription factors in leukemic cells states, including the leukemia genome-wide association study hit ELK3. The accompanying gene expression changes associated with natural killer cell inactivation and depletion in the leukemic immune microenvironment. Moreover, our results suggest that the abundance of G1 cell cycle state at diagnosis and lack of differentiation-associated regulatory network changes during induction chemotherapy represent features of chemoresistance. To target the leukemic regulatory program and thereby overcome treatment resistance, we show that inhibition of ETS-transcription factors reduced cell viability and resolved pathways contributing to this using scRNA-seq. Conclusions Our data provide a detailed picture of the transcription factor activities characterizing both normal B-lineage differentiation and those acquired in leukemic bone marrow and provide a rational basis for new treatment strategies targeting the immune microenvironment and the active regulatory network in leukemia.

scholarly journals AP1 Transcription Factors in Epidermal Differentiation and Skin Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Richard L. Eckert ◽  
Gautam Adhikary ◽  
Christina A. Young ◽  
Ralph Jans ◽  
James F. Crish ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Dominant Negative ◽  
Epidermal Differentiation ◽  
Cancer Development ◽  
Multiple Cells ◽  
Different Levels ◽  
Factor Function

AP1 (jun/fos) transcription factors (c-jun, junB, junD, c-fos, FosB, Fra-1, and Fra-2) are key regulators of epidermal keratinocyte survival and differentiation and important drivers of cancer development. Understanding the role of these factors in epidermis is complicated by the fact that each protein is expressed, at different levels, in multiple cells layers in differentiating epidermis, and because AP1 transcription factors regulate competing processes (i.e., proliferation, apoptosis, and differentiation). Variousin vivogenetic approaches have been used to study these proteins including targeted and conditional knockdown, overexpression, and expression of dominant-negative inactivating AP1 transcription factors in epidermis. Taken together, these studies suggest that individual AP1 transcription factors have different functions in the epidermis and in cancer development and that altering AP1 transcription factor function in the basal versus suprabasal layers differentially influences the epidermal differentiation response and disease and cancer development.

scholarly journals Single cell characterization of B-lymphoid differentiation and leukemic cell states during chemotherapy in ETV6-RUNX1 positive pediatric leukemia identifies drug-targetable transcription factor activities

2020 ◽  
Author(s):  
Juha Mehtonen ◽  
Susanna Teppo ◽  
Mari Lahnalampi ◽  
Aleksi Kokko ◽  
Riina Kaukonen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Regulatory Network ◽  
Leukemic Cell ◽  
Immune Microenvironment ◽  
Ets Transcription Factors ◽  
Lineage Differentiation ◽  
B Lineage

AbstractTight regulatory loops orchestrate commitment to B-cell fate within bone marrow. Genetic lesions in this gene regulatory network underlie the emergence of the most common childhood cancer, acute lymphoblastic leukemia (ALL). The initial genetic hits, including the common translocation that fuses ETV6 and RUNX1 genes, lead to arrested cell differentiation. Here, we aimed to characterize transcription factor activities along the B-lineage differentiation trajectory as a reference to characterize the aberrant cell states present in leukemic bone marrow, and to identify those transcription factors that maintain cancer-specific cell states for more precise therapeutic intervention.We compared normal B-lineage differentiation and in vivo leukemic cell states using single cell RNA-sequencing (scRNA-seq) and several complementary genomics profiles. Based on statistical tools for scRNA-seq, we benchmarked a workflow to resolve transcription factor activities and gene expression distribution changes in healthy bone marrow lymphoid cell states. We compared these to ALL bone marrow at diagnosis and in vivo during chemotherapy, focusing on leukemias carrying the ETV6-RUNX1 fusion.We show that lymphoid cell transcription factor activities uncovered from bone marrow scRNA-seq have high correspondence with independent ATAC- and ChIP-seq data. Using this comprehensive reference for regulatory factors coordinating B-lineage differentiation, our analysis of ETV6-RUNX1-positive ALL cases revealed elevated activity of multiple ETS-transcription factors in leukemic cells states, including the leukemia genome-wide association study hit ELK3. The accompanying gene expression changes associated with natural killer cell inactivation and depletion in the leukemic immune microenvironment. Moreover, our results suggest that the abundance of G1 cell cycle state at diagnosis and lack of differentiation-associated regulatory network changes during induction chemotherapy represent features of chemoresistance. To target the leukemic regulatory program and thereby overcome treatment-resistance, we show that selective inhibitors of ETS-transcription factors could effectively reduce cell viability.Our data provide a detailed picture of the transcription factor activities that characterize both normal B-lineage differentiation and those acquired in leukemic bone marrow and provide a rational basis for new treatment strategies targeting the immune microenvironment and the active regulatory network in leukemia.

Abstract 239: Selective Class I and II Histone Deacetylation Inhibitors Alter Stability of HDAC-Corepressor Complexes

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Hsiao C Wang ◽  
Lillianne G Harris ◽  
James C Chou ◽  
Santhosh Mani ◽  
Donald Menick
Keyword(s):  
Heart Failure ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cardiac Hypertrophy ◽  
Critical Role ◽  
Hdac Inhibitors ◽  
Class I ◽  
Proximal Promoter ◽  
Repressor Complex ◽  
The Stability

Introduction: Alterations in expression and activity of different genes have been implicated in the pathogenesis of heart failure. Our lab has shown that HDAC-repressor complexes play a critical role in the upregulation Sodium Calcium Exchanger ( Ncx1) and HDAC inhibition causes changes that attenuated cardiac remodeling during cardiac hypertrophy and heart failure. Thus, treatment with HDAC inhibitors has been proposed as a potential strategy for treatment of cardiac hypertrophy and heart failure. HDAC inhibitors repress deacetylase activity but we propose that they also affect HDAC confirmation and interaction with other protein factors. We hypothesize that HDAC inhibitors affect the stability of the co-repressor complex with specific transcription factors and that this effect is dependent on the transcription factor. Results: Inhibition of HDACs in adult cardiomyocytes results in the greater stabilization of HDACs with co-repressor molecules that were recruited to the NCX1 promoter through Nkx2.5 transcription factor. HDAC class I specific inhibitor, MS 275 demonstrated stronger association between HDACs and co-repressors while other Class I inhibitors, PD106 and BML 210 failed on showing this phenomenal. The results suggested that class I HDACs inhibitors may affect formations of HDAC-complex via alternated active site interactions other than chelating with zinc binding domain. These results compliment ChIP experiments which also demonstrate the different recruitments of Sin3a at the proximal promoter of NCX1. In vivo analysis on HDAC5 knockout mice reveal that the Sin3a-HDAC1/2 repressor complex is not recruited to the Ncx1 promoter in the absence of HDAC5, indicating not only Class I HDAC but also Class II HDACs play an important role on HDAC-complex formation. Conclusions: This work gives insight into part of the molecular mechanism of how HDAC inhibitors can affect the stability of the HDAC co-repressor complex in cardiac hypertrophy and heart failure. In addition, we demonstrated the Class IIa HDACs are required for the recruitment of the Sin3a/HDAC1/2 co-repressor complex to specific transcription factors on the target promoter.

scholarly journals The NAC-type transcription factor CaNAC46 regulates the salt and drought tolerance of transgenic Arabidopsis thaliana

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Ma ◽  
Li-yue Wang ◽  
Jia-xi Dai ◽  
Ying Wang ◽  
Duo Lin
Keyword(s):  
Arabidopsis Thaliana ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Drought Tolerance ◽  
Abiotic Stresses ◽  
Lateral Roots ◽  
High Salt ◽  
Wild Type ◽  
Ros Scavenging ◽  
Drought And Salt Stresses

Abstract Background The NAC (NAM, ATAF1/ATAF2, and CUC2) transcription factors belong to a large family of plant-specific transcription factors in monocot and dicot species. These transcription factors regulate the expression of stress tolerance-related genes that protect plants from various abiotic stresses, including drought, salinity, and low temperatures. Results In this study, we identified the CaNAC46 transcription factor gene in Capsicum annuum. Its open reading frame was revealed to comprise 921 bp, encoding a protein consisting of 306 amino acids, with an isoelectric point of 6.96. A phylogenetic analysis indicated that CaNAC46 belongs to the ATAF subfamily. The expression of CaNAC46 was induced by heat, cold, high salt, drought, abscisic acid, salicylic acid, and methyl jasmonate treatments. Thus, CaNAC46 may be important for the resistance of dry pepper to abiotic stresses. A subcellular localization analysis confirmed that CaNAC46 is localized in the nucleus. The overexpression of CaNAC46 improved the tolerance of transgenic Arabidopsis thaliana plants to drought and salt stresses. The CaNAC46-overexpressing lines had longer roots and more lateral roots than wild-type lines under prolonged drought and high salt stress conditions. Additionally, CaNAC46 affected the accumulation of reactive oxygen species (ROS). Moreover, CaNAC46 promoted the expression of SOD, POD, RD29B, RD20, LDB18, ABI, IAA4, and P5CS. The malondialdehyde contents were higher in TRV2-CaNAC46 lines than in wild-type plants in response to drought and salt stresses. Furthermore, the expression levels of stress-responsive genes, such as ABA2, P5CS, DREB, RD22, CAT, and POD, were down-regulated in TRV2-CaNAC46 plants. Conclusions Under saline and drought conditions, CaNAC46 is a positive regulator that activates ROS-scavenging enzymes and enhances root formation. The results of our study indicate CaNAC46 is a transcriptional regulator responsible for salinity and drought tolerance and suggest the abiotic stress-related gene regulatory mechanisms controlling this NAC transcription factor are conserved between A. thaliana and pepper.

scholarly journals AtCIPK16 Mediates Salt Stress Through Phytohormones and Transcription Factors

2020 ◽  
Author(s):  
Shanika L. Amarasinghe ◽  
Wenmian Huang ◽  
Nathan S. Watson-Haigh ◽  
Matthew Gilliham ◽  
Stuart J. Roy ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Salt Stress ◽  
Salt Tolerance ◽  
Salinity Tolerance ◽  
Food Production ◽  
Rna Seq ◽  
Productivity Losses ◽  
Global Food

AbstractSoil salinity causes large productivity losses for agriculture worldwide. “Next-generation crops” that can tolerate salt stress are required for the sustainability of global food production. Previous research in Arabidopsis thaliana aimed at uncovering novel factors underpinning improved plant salinity tolerance identified the protein kinase AtCIPK16. Overexpression of AtCIPK16 enhanced shoot Na+ exclusion and increased biomass in both Arabidopsis and barley. Here, a comparative transcriptomic study on Arabidopsis lines expressing AtCIPK16 was conducted in the presence and absence of salt stress, using an RNA-Seq approach, complemented by AtCIPK16 interaction and localisation studies. We are now able to provide evidence for AtCIPK16 activity in the nucleus. Moreover, the results manifest the involvement of a transcription factor, AtTZF1, phytohormones and the ability to quickly reach homeostasis as components important for improving salinity tolerance in transgenics overexpressing AtCIPK16. Furthermore, we suggest the possibility of both biotic and abiotic tolerance through AtCIPK16, and propose a model for the salt tolerance pathway elicited through AtCIPK16.

scholarly journals Genomic Retargeting of Tumor Suppressors p53 and CTCF Promotes Oncogenesis

2019 ◽  
Author(s):  
Michal Schwartz ◽  
Avital Sarusi Portugez ◽  
Bracha Zukerman Attia ◽  
Miriam Tannenbaum ◽  
Olga Loza ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Tumor Suppressors ◽  
Regulatory Network ◽  
Regulatory Elements ◽  
Cancer Development ◽  
Chromatin Binding ◽  
Transcriptional Reprogramming ◽  
Major Variation ◽  
Regulatory Landscape

AbstractGene transcription is substantially regulated by distant regulatory elements via combinatorial binding of transcription factors. It is more and more recognized that alterations in chromatin state and transcription factor binding in these distant regulatory elements may have key roles in cancer development. Here we focused on the first stages of oncogene induced carcinogenic transformation, and characterized the regulatory network underlying transcriptional reprogramming associated with this process. Using Hi-C data, we couple between differentially expressed genes and their differentially active regulatory elements and reveal two candidate transcription factors, p53 and CTCF, as major determinants of transcriptional reprogramming at early stages of HRas-induced transformation. Strikingly, the malignant transcriptional reprograming is promoted by redistribution of chromatin binding of these factors without major variation in their expression level. Our results demonstrate that alterations in the regulatory landscape have a major role in driving oncogene-induced transcriptional reprogramming.

scholarly journals Local DNA shape is a general principle of transcription factor binding specificity in Arabidopsis thaliana

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Janik Sielemann ◽  
Donat Wulf ◽  
Romy Schmidt ◽  
Andrea Bräutigam
Keyword(s):  
Machine Learning ◽  
Arabidopsis Thaliana ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Dna Binding ◽  
Transcription Factor Binding ◽  
Binding Prediction ◽  
Factor Binding ◽  
A Genome ◽  
Dna Shape

AbstractUnderstanding gene expression will require understanding where regulatory factors bind genomic DNA. The frequently used sequence-based motifs of protein-DNA binding are not predictive, since a genome contains many more binding sites than are actually bound and transcription factors of the same family share similar DNA-binding motifs. Traditionally, these motifs only depict sequence but neglect DNA shape. Since shape may contribute non-linearly and combinational to binding, machine learning approaches ought to be able to better predict transcription factor binding. Here we show that a random forest machine learning approach, which incorporates the 3D-shape of DNA, enhances binding prediction for all 216 tested Arabidopsis thaliana transcription factors and improves the resolution of differential binding by transcription factor family members which share the same binding motif. We observed that DNA shape features were individually weighted for each transcription factor, even if they shared the same binding sequence.

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