scholarly journals iFORM: incorporating Find Occurrence of Regulatory Motifs

2016 ◽  
Author(s):  
Chao Ren ◽  
Hebing Chen ◽  
Feng Liu ◽  
Hao Li ◽  
Xiaochen Bo ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Dna Sequence ◽  
Binding Sites ◽  
Human Disease ◽  
Motif Discovery ◽  
Encode Project ◽  
Regulatory Motifs ◽  
Nih Roadmap ◽  
Fisher’S Combined Probability Test

Accurately identifying binding sites of transcription factors (TFs) is crucial to understand the mechanisms of transcriptional regulation and human disease. We present incorporating Find Occurrence of Regulatory Motifs (iFORM), an easy-to-use tool for scanning DNA sequence with TF motifs described as position weight matrices (PWMs). iFORM achieves higher accuracy and sensitivity by integrating the results from five classical motif discovery programs based on Fisher's combined probability test. We have used iFORM to provide accurate results on a variety of data in the ENCODE Project and the NIH Roadmap Epigenomics Project, and has demonstrated its utility to further understand individual roles of functional elements.iFORM can be freely accessed athttps://github.com/wenjiegroup/iFORM.

scholarly journals The histone variant H2A.Z and chromatin remodeler BRAHMA act coordinately and antagonistically to regulate transcription and nucleosome dynamics in Arabidopsis

2018 ◽  
Author(s):  
E. Shannon Torres ◽  
Roger B. Deal
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Binding Sites ◽  
Transcriptional Repression ◽  
Nucleosome Positioning ◽  
Chromatin Organization ◽  
Histone H2a ◽  
Nucleosome Dynamics ◽  
Environmentally Responsive ◽  
Context Specific

ABSTRACTPlants adapt to changes in their environment by regulating transcription and chromatin organization. The histone H2A variant H2A.Z and the SWI2/SNF2 ATPase BRAHMA have overlapping roles in positively and negatively regulating environmentally responsive genes in Arabidopsis, but the extent of this overlap was uncharacterized. Both have been associated with various changes in nucleosome positioning and stability in different contexts, but their specific roles in transcriptional regulation and chromatin organization need further characterization. We show that H2A.Z and BRM act both cooperatively and antagonistically to contribute directly to transcriptional repression and activation of genes involved in development and response to environmental stimuli. We identified 8 classes of genes that show distinct relationships between H2A.Z and BRM and their roles in transcription. We found that H2A.Z contributes to a range of different nucleosome properties, while BRM stabilizes nucleosomes where it binds and destabilizes and/or repositions flanking nucleosomes. H2A.Z and BRM contribute to +1 nucleosome destabilization, especially where they coordinately regulate transcription. We also found that at genes regulated by both BRM and H2A.Z, both factors overlap with the binding sites of light-regulated transcription factors PIF4, PIF5, and FRS9, and that some of the FRS9 binding sites are dependent on H2A.Z and BRM for accessibility. Collectively, we comprehensively characterized the antagonistic and cooperative contributions of H2A.Z and BRM to transcriptional regulation, and illuminated their interrelated roles in chromatin organization. The variability observed in their individual functions implies that both BRM and H2A.Z have more context-specific roles within diverse chromatin environments than previously assumed.

scholarly journals ProSampler: an ultrafast and accurate motif finder in large ChIP-seq datasets for combinatory motif discovery

2019 ◽  
Vol 35 (22) ◽  
pp. 4632-4639 ◽  
Author(s):  
Yang Li ◽  
Pengyu Ni ◽  
Shaoqiang Zhang ◽  
Guojun Li ◽  
Zhengchang Su
Keyword(s):  
Transcription Factors ◽  
Gibbs Sampler ◽  
Binding Sites ◽  
Motif Discovery ◽  
Source Code ◽  
Motif Finding ◽  
Supplementary Information ◽  
Highly Efficient ◽  
Motif Finder ◽  
Motif Finding Algorithm

Abstract Motivation The availability of numerous ChIP-seq datasets for transcription factors (TF) has provided an unprecedented opportunity to identify all TF binding sites in genomes. However, the progress has been hindered by the lack of a highly efficient and accurate tool to find not only the target motifs, but also cooperative motifs in very big datasets. Results We herein present an ultrafast and accurate motif-finding algorithm, ProSampler, based on a novel numeration method and Gibbs sampler. ProSampler runs orders of magnitude faster than the fastest existing tools while often more accurately identifying motifs of both the target TFs and cooperators. Thus, ProSampler can greatly facilitate the efforts to identify the entire cis-regulatory code in genomes. Availability and implementation Source code and binaries are freely available for download at https://github.com/zhengchangsulab/prosampler. It was implemented in C++ and supported on Linux, macOS and MS Windows platforms. Supplementary information Supplementary materials are available at Bioinformatics online.

scholarly journals Transcriptional Regulation in the G1-S Cell Cycle Stage in Fungi: Insights through Computational Analysis

2012 ◽  
Vol 6 (1) ◽  
pp. 43-54
Author(s):  
Viktor Martyanov ◽  
Robert H. Gross
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Dna Sequences ◽  
Binding Sites ◽  
Positional Distribution ◽  
Upstream Sequence ◽  
Regulatory Pathways ◽  
Binding Factor

The transcription factor complexes Mlu1-box binding factor (MBF) and Swi4/6 cell cycle box binding factor (SBF) regulate the cell cycle in Saccharomyces cerevisiae. They activate hundreds of genes and are responsible for nor-mal cell cycle progression from G1 to S phase. We investigated the conservation of MBF and SBF binding sites during fungal evolution. Orthologs of S. cerevisiae targets of these transcription factors were identified in 37 fungal species and their upstream regions were analyzed for putative transcription factor binding sites. Both groups displayed enrichment in specific putative regulatory DNA sequences in their upstream regions and showed different preferred upstream motif loca-tions, variable patterns of evolutionary conservation of the motifs and enrichment in unique biological functions for the regulated genes. The results indicate that despite high sequence similarity of upstream DNA motifs putatively associated with G1-S transcriptional regulation by MBF and SBF transcription factors, there are important upstream sequence feature differences that may help differentiate the two seemingly similar regulatory modes. The incorporation of upstream motif sequence comparison, positional distribution and evolutionary variability of the motif can complement functional infor-mation about roles of the respective gene products and help elucidate transcriptional regulatory pathways and functions.

Mechanisms of Transcriptional Regulation and Transformation by HOXA9

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. SCI-30-SCI-30
Author(s):  
Jay L. Hess ◽  
Cailin Collins ◽  
Joel Bronstein ◽  
Yuqing Sun ◽  
Surya Nagaraja
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Target Genes ◽  
Conflicts Of Interest ◽  
Hematopoietic Stem ◽  
A Genome ◽  
The Impact

Abstract Abstract SCI-30 HOXA9 plays important roles in both development and hematopoiesis and is overexpressed in more than 50 percent of acute myeloid leukemias (AML). Nearly all cases of AML with mixed lineage leukemia (MLL) translocations show increased HOXA9 expression, as well as cases with mutation of the nucleophosmin gene NPM1, overexpression of CDX2, and fusions of NUP98. In most cases, upregulation of HOXA9 is accompanied by upregulation of its homeodomain-containing cofactor MEIS1, which directly interacts with HOXA9. While HOXA9 alone is sufficient for transformation of hematopoietic stem cells in culture, the addition of MEIS1 increases the transformation efficiency and results in rapidly fatal leukemias in transplanted animals. Despite the crucial role that HOXA9 plays in development, hematopoiesis, and leukemia, its transcriptional targets and mechanisms of action are poorly understood. We have used ChIP-seq to identify Hoxa9 and Meis1 binding sites on a genome-wide level in myeloblastic cells, profiled their associated epigenetic modifications, identified the target genes regulated by HOXA9 and identified HOXA9 interacting proteins. HOXA9 and MEIS1 cobind at hundreds of promoter distal, highly evolutionarily conserved sites showing high levels of histone H3K4 monomethylation and CBP/P300 binding. These include many proleukemogenic gene loci, such as Erg, Flt3, Myb, Lmo2, and Sox4. In addition, HOXA9 binding sites overlap a subset of enhancers previously implicated in myeloid differentiation and inflammation. HOXA9 binding at enhancers stabilizes association of MEIS1 and lineage-restricted transcription factors, including C/EBPα, PU.1, and STAT5A/B thereby promoting CBP/p300 recruitment, histone acetylation, and transcriptional activation. Current efforts are focused on using both biochemical and genetic approaches to assess the role of HOXA9 “enhanceosome” components C/EBPα, PU.1, and STAT5A/B in transcriptional regulation and leukemogenesis. Studies to date suggest that C/EBPα and PU.1 binding can occur in the absence of HOXA9/MEIS1, supporting a model in which these proteins act as pioneer transcription factors for establishment of poised, but not activated, HOXA9-regulated enhancers. Work is under way to assess the impact of high-level HOXA9 and MEIS1 on enhanceosome assembly and the role of recruitment of transcriptional coactivators involved in target gene up- or downregulation, including histone acetyltransferases and chromatin remodeling complexes. Collectively, our findings suggest that HOXA9-regulated enhancers are a fundamental mechanism of HOX-mediated transcription in normal development that is deregulated in leukemia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Beyond Trees: Regulons and Regulatory Motif Characterization

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 995
Author(s):  
Xuhua Xia
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Target Genes ◽  
Biological Function ◽  
Regulatory Motifs ◽  
Candidate Target ◽  
Tree Genetics ◽  
Growth And Reproduction

Trees and their seeds regulate their germination, growth, and reproduction in response to environmental stimuli. These stimuli, through signal transduction, trigger transcription factors that alter the expression of various genes leading to the unfolding of the genetic program. A regulon is conceptually defined as a set of target genes regulated by a transcription factor by physically binding to regulatory motifs to accomplish a specific biological function, such as the CO-FT regulon for flowering timing and fall growth cessation in trees. Only with a clear characterization of regulatory motifs, can candidate target genes be experimentally validated, but motif characterization represents the weakest feature of regulon research, especially in tree genetics. I review here relevant experimental and bioinformatics approaches in characterizing transcription factors and their binding sites, outline problems in tree regulon research, and demonstrate how transcription factor databases can be effectively used to aid the characterization of tree regulons.

scholarly journals Prediction of regulatory motifs from human Chip-sequencing data using a deep learning framework

2019 ◽  
Vol 47 (15) ◽  
pp. 7809-7824 ◽  
Author(s):  
Jinyu Yang ◽  
Anjun Ma ◽  
Adam D Hoppe ◽  
Cankun Wang ◽  
Yang Li ◽  
...  
Keyword(s):  
Deep Learning ◽  
Dna Binding ◽  
Binding Sites ◽  
Motif Discovery ◽  
Distribution Model ◽  
Sequencing Data ◽  
Shape Information ◽  
Chip Sequencing ◽  
Regulatory Motifs ◽  
Learning Framework

Abstract The identification of transcription factor binding sites and cis-regulatory motifs is a frontier whereupon the rules governing protein–DNA binding are being revealed. Here, we developed a new method (DEep Sequence and Shape mOtif or DESSO) for cis-regulatory motif prediction using deep neural networks and the binomial distribution model. DESSO outperformed existing tools, including DeepBind, in predicting motifs in 690 human ENCODE ChIP-sequencing datasets. Furthermore, the deep-learning framework of DESSO expanded motif discovery beyond the state-of-the-art by allowing the identification of known and new protein–protein–DNA tethering interactions in human transcription factors (TFs). Specifically, 61 putative tethering interactions were identified among the 100 TFs expressed in the K562 cell line. In this work, the power of DESSO was further expanded by integrating the detection of DNA shape features. We found that shape information has strong predictive power for TF–DNA binding and provides new putative shape motif information for human TFs. Thus, DESSO improves in the identification and structural analysis of TF binding sites, by integrating the complexities of DNA binding into a deep-learning framework.

BMP and WNT-Directed Transcription Factors TCF7L2/TCF4 and SMAD1 Bind to Distinct Hematopoietic-Specific Target Genes Depending on Cell Lineage

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3870-3870
Author(s):  
Eirini Trompouki ◽  
Teresa V. Bowman ◽  
Lee N Lawton ◽  
Zi Peng Fan ◽  
Anthony DiBiase ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Signaling Pathways ◽  
Binding Sites ◽  
Motif Discovery ◽  
Target Genes ◽  
Cell Lineage ◽  
K562 Cells ◽  
Cell Type ◽  
Advisory Committees ◽  
Equity Ownership

Abstract Abstract 3870 The BMP and WNT signaling pathways are two highly conserved signaling pathways that cooperate in many developmental processes, ultimately through alteration of transcription via SMAD and TCF transcription factors. These pathways elicit pleiotropic outcomes across cell types, yet only a few cell-specific direct target genes are known for the signaling transcription factors that mitigate these effects. We took a genome-wide approach to define the binding sites of BMP and WNT-directed transcription factors in different hematopoietic lineages. Using heat-shock inducible transgenic fish lines that overexpress BMP2 or WNT8, we demonstrated accelerated marrow recovery following irradiation. Irradiation recovery was blunted by heat shock induced overexpression of the respective inhibitors Chordin and DKK1. Similar to the zebrafish regeneration results, competitive transplants with mouse bone marrow treated with the WNT agonist BIO led to enhanced chimerism. Inhibition of BMP diminished peripheral blood contribution even in the presence of WNT stimulation, suggesting a conserved and cell intrinsic interaction for these signaling pathways in adult stress hematopoiesis. To examine potential target genes that could account for the synergy, we performed chromatin immunoprecipitation with WNT- and BMP-activated transcription factors followed by sequencing (ChIP-seq) in K562 cells. ChIP-seq was performed with TCF7L2/TCF4, a mediator of the WNT pathway, and SMAD1, a mediator of the BMP signaling pathway, and >2000 binding sites were identified for each factor. Motif discovery revealed that the DNA sequences bound by TCF7L2 and SMAD1 were not only enriched for TCF and SMAD binding elements, respectively, but were also enriched for a GATA motif. Comparison of the TCF7L2 and SMAD1 bound genes with published ChIP-Seq data for GATA1 and GATA2 in K562 cells revealed that both signaling factors bind more than 40% of GATA1 bound genes and greater than 70% of GATA2 bound genes. Ingenuity and GSEA analysis revealed that genes important for erythropoiesis were among the genes co-bound by these factors. To evaluate the effect of cell lineage on signaling factor binding, ChIP-seq of TCF7L2 and SMAD1 in U937, a monocytic leukemia cell line, was performed. Motif discovery of sequences bound in U937 found enrichment for an ETS motif, which is bound by the key myeloid transcription factor Pu.1. In addition, TCF7L2 and SMAD1 bound genes in U937 overlapped genes bound by C/EBPalpha in U937 by greater than 70%. These genes are implicated in monocytic development. The overlap of binding between TCF7L2 in K562 and U937 was less than 15% and the overlap of SMAD1 binding sites between the cell lines was less than 10%, indicating a substantial influence of cell lineage on transcription factor binding. Confirmation of cell type selective binding of TCF7L2 and SMAD1 in vivo was accomplished by ChIP of the transcription factors in zebrafish nucleated erythrocytes. Binding of TCF7L2 and SMAD1 in these cells showed that these factors co-bind with GATA1 in many genes with established roles in erythropoiesis. Together our data suggest the co-binding of WNT- and BMP-specific transcription factors with master regulators of each hematopoietic cell type results in regulation of distinct blood genes based on lineage. (First two authors contributed equally to this work) Disclosures: Zon: FATE, Inc.: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Stemgent: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Evolutionarily Conserved Transcription Factors Drive the Oxidative Stress Response in Drosophila

2019 ◽  
Author(s):  
Sarah M. Ryan ◽  
Kaitie Wildman ◽  
Briseida Oceguera-Perez ◽  
Scott Barbee ◽  
Nathan T. Mortimer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Stress Response ◽  
Comparative Genomics ◽  
Gene Family ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Binding Sites ◽  
Regulatory Elements

AbstractAs organisms are constantly exposed to the damaging effects of oxidative stress through both environmental exposure as well as internal metabolic processes, they have evolved a variety of mechanisms to cope with this stress. One such mechanism is the highly conserved p38 MAPK (p38K) pathway, which is known to be to post-translationally activated in response to oxidative stress resulting in the activation of downstream antioxidant targets. However, little is known about the role of p38K transcriptional regulation in response to oxidative stress. Therefore, we analyzed the p38K gene family across the genus Drosophila to identify conserved regulatory elements. We find that oxidative stress exposure results in increased p38K protein levels in multiple Drosophila species and is associated with increased oxidative stress resistance. We also find that the p38Kb genomic locus includes conserved binding sites for the AP-1 and lola-PT transcription factors. Accordingly, over-expression of these transcription factors in D. melanogaster is sufficient to induce transcription of p38Kb and enhances resistance to oxidative stress. We further find that the presence of a lola-PT binding site in the p38Kb locus of a given species is predictive of the species’ survival in response to oxidative stress. Through our comparative genomics approach, we have identified biologically relevant transcription factor binding sites that regulate the expression of p38Kb and are associated with resistance to oxidative stress. These findings reveal a novel mode of regulation for p38K genes and suggests that transcription may play as important a role in p38K mediated stress responses as post-translational modifications.Significance StatementOrganisms encounter a variety of environmental stresses such as oxidative stress throughout their lifetime. Therefore, organisms have evolved a number of mechanisms to combat these stresses. In order to understand how these mechanisms evolved, we have compared the genomes of a diverse set of species across the genus Drosophila to examine the p38 MAPK stress response gene family. Our analysis was able to successfully predict transcription factors that not only regulate our target gene, p38Kb, but do so under different conditions to ensure an appropriate stress response. Therefore, we find that in addition to post-translational regulation, transcriptional regulation of signaling pathways may also play an important role in how organisms are able to adapt to stressful environments or respond to stress conditions as they arise. Furthermore, our comparative genomics approach may be utilized to identify transcriptional regulators of other highly conserved signaling pathways.

scholarly journals CTCF As an Example of DNA-Binding Transcription Factors Containing Clusters of C2H2-Type Zinc Fingers

Acta Naturae ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 31-46
Author(s):  
Oksana G. Maksimenko ◽  
Dariya V. Fursenko ◽  
Elena V. Belova ◽  
Pavel G. Georgiev
Keyword(s):  
Experimental Data ◽  
Transcription Factors ◽  
Dna Binding ◽  
Characteristic Feature ◽  
Dna Sequence ◽  
Binding Sites ◽  
Zinc Fingers ◽  
Topologically Associating Domains ◽  
Key Factor

In mammals, most of the boundaries of topologically associating domains and all well-studied insulators are rich in binding sites for the CTCF protein. According to existing experimental data, CTCF is a key factor in the organization of the architecture of mammalian chromosomes. A characteristic feature of the CTCF is that the central part of the protein contains a cluster consisting of eleven domains of C2H2-type zinc fingers, five of which specifically bind to a long DNA sequence conserved in most animals. The class of transcription factors that carry a cluster of C2H2-type zinc fingers consisting of five or more domains (C2H2 proteins) is widely represented in all groups of animals. The functions of most C2H2 proteins still remain unknown. This review presents data on the structure and possible functions of these proteins, using the example of the vertebrate CTCF protein and several well- characterized C2H2 proteins in Drosophila and mammals.

Sign in / Sign up

Export Citation Format

Share Document