Genome-wide similarity search for transcription factors and their binding sites in a metal-reducing prokaryote Geobacter sulfurreducens

Biosystems ◽  
2007 ◽  
Vol 90 (2) ◽  
pp. 421-441 ◽  
Author(s):  
Bin Yan ◽  
Derek R. Lovley ◽  
Julia Krushkal
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Similarity Search ◽  
Geobacter Sulfurreducens ◽  
Genome Wide

scholarly journals TFutils: Data structures for transcription factor bioinformatics

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 152
Author(s):  
Benjamin J. Stubbs ◽  
Shweta Gopaulakrishnan ◽  
Kimberly Glass ◽  
Nathalie Pochet ◽  
Celine Everaert ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Data Structures ◽  
Binding Sites ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Bioconductor Package ◽  
Genome Wide ◽  
Study Results ◽  
Integrative Analyses

DNA transcription is intrinsically complex. Bioinformatic work with transcription factors (TFs) is complicated by a multiplicity of data resources and annotations. The Bioconductor package TFutils includes data structures and functions to enhance the precision and utility of integrative analyses that have components involving TFs. TFutils provides catalogs of human TFs from three reference sources (CISBP, HOCOMOCO, and GO), a catalog of TF targets derived from MSigDb, and multiple approaches to enumerating TF binding sites. Aspects of integration of TF binding patterns and genome-wide association study results are explored in examples.

scholarly journals Genome-wide binding of posterior HOXA/D transcription factors reveals subgrouping and association with CTCF

2016 ◽  
Author(s):  
Ivana Jerković ◽  
Daniel M. Ibrahim ◽  
Guillaume Andrey ◽  
Stefan Haas ◽  
Peter Hansen ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Hox Genes ◽  
Ctcf Binding ◽  
Proximity Ligation Assay ◽  
Homeotic Genes ◽  
Sequence Specificity ◽  
Individual Genome ◽  
Genome Wide ◽  
Group 1

AbstractHomeotic genes code for key transcription factors (HOX-TFs) that pattern the animal body plan. During embryonic development, Hox genes are expressed in overlapping patterns and function in a partially redundant manner. In vitro biochemical screens probing the HOX-TF sequence specificity revealed largely overlapping sequence preferences, indicating that co-factors might modulate the biological function of HOX-TFs. However, due to their overlapping expression pattern, high protein homology, and insufficiently specific antibodies, little is known about their genome-wide binding preferences. In order to overcome this problem, we virally expressed tagged versions of limb-expressed posterior Hox genes (Hoxa9-13, and Hoxd9-13) in primary mesenchymal limb progenitor cells (micromass). We determined the effect of each HOX-TF on cellular differentiation (chondrogenesis) and gene expression and found that groups of HOX-TFs induce distinct regulatory programs. We used ChIP-seq to determine their individual genome-wide binding profiles and identified between 12,540 and 27,466 binding sites for each of the nine HOX-TFs. Principal Component Analysis (PCA) of binding profiles revealed that the HOX-TFs are clustered in two subgroups (Group 1: HOXA/D9, HOXA/D10, HOXD12, and HOXA13 and Group 2: HOXA/D11 and HOXD13), which are characterized by differences in their sequence specificity and by the presence of cofactor motifs. Specifically, we identified CTCF binding sites in Group 1, indicating that this subgroup of HOX-proteins cooperates with CTcf. We confirmed this interaction by an independent biological assay (proximity ligation assay) and showed that CTCF is a novel HOX cofactor that specifically associates with Group 1 HOX-TFs, pointing towards a possible interplay between HOX-TFs and chromatin architecture.

scholarly journals Comparing the epigenetic landscape in myonuclei purified with a PCM1 antibody from a fast/glycolytic and a slow/oxidative muscle

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009907
Author(s):  
Mads Bengtsen ◽  
Ivan Myhre Winje ◽  
Einar Eftestøl ◽  
Johannes Landskron ◽  
Chengyi Sun ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Association Studies ◽  
Cell Types ◽  
Specific Marker ◽  
Fiber Types ◽  
Epigenetic Landscape ◽  
Genome Wide ◽  
A Genome ◽  
Pericentriolar Material

Muscle cells have different phenotypes adapted to different usage, and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of the epigenetic landscape by ChIP-Seq in two muscle extremes, the fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where up to 60% of the nuclei can be of a different origin. Since cellular homogeneity is critical in epigenome-wide association studies we developed a new method for purifying skeletal muscle nuclei from whole tissue, based on the nuclear envelope protein Pericentriolar material 1 (PCM1) being a specific marker for myonuclei. Using antibody labelling and a magnetic-assisted sorting approach, we were able to sort out myonuclei with 95% purity in muscles from mice, rats and humans. The sorting eliminated influence from the other cell types in the tissue and improved the myo-specific signal. A genome-wide comparison of the epigenetic landscape in EDL and soleus reflected the differences in the functional properties of the two muscles, and revealed distinct regulatory programs involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles were also regulated by different sets of transcription factors; e.g. in soleus, binding sites for MEF2C, NFATC2 and PPARA were enriched, while in EDL MYOD1 and SIX1 binding sites were found to be overrepresented. In addition, more novel transcription factors for muscle regulation such as members of the MAF family, ZFX and ZBTB14 were identified.

scholarly journals FOXA2 regulates a network of genes involved in critical functions of human intestinal epithelial cells

2015 ◽  
Vol 47 (7) ◽  
pp. 290-297 ◽  
Author(s):  
Nehal Gosalia ◽  
Rui Yang ◽  
Jenny L. Kerschner ◽  
Ann Harris
Keyword(s):  
Transcription Factors ◽  
Epithelial Cell ◽  
Binding Sites ◽  
Intestinal Epithelial Cell ◽  
Cell Function ◽  
Mrna Levels ◽  
Intestinal Epithelial ◽  
Membrane Function ◽  
Protein Levels ◽  
Genome Wide

The forkhead box A (FOXA) family of pioneer transcription factors is critical for the development of many endoderm-derived tissues. Their importance in regulating biological processes in the lung and liver is extensively characterized, though much less is known about their role in intestine. Here we investigate the contribution of FOXA2 to coordinating intestinal epithelial cell function using postconfluent Caco2 cells, differentiated into an enterocyte-like model. FOXA2 binding sites genome-wide were determined by ChIP-seq and direct targets of the factor were validated by ChIP-qPCR and siRNA-mediated depletion of FOXA1/2 followed by RT-qPCR. Peaks of FOXA2 occupancy were frequent at loci contributing to gene ontology pathways of regulation of cell migration, cell motion, and plasma membrane function. Depletion of both FOXA1 and FOXA2 led to a significant reduction in the expression of multiple transmembrane proteins including ion channels and transporters, which form a network that is essential for maintaining normal ion and solute transport. One of the targets was the adenosine A2B receptor, and reduced receptor mRNA levels were associated with a functional decrease in intracellular cyclic AMP. We also observed that 30% of FOXA2 binding sites contained a GATA motif and that FOXA1/A2 depletion reduced GATA-4, but not GATA-6 protein levels. These data show that FOXA2 plays a pivotal role in regulating intestinal epithelial cell function. Moreover, that the FOXA and GATA families of transcription factors may work cooperatively to regulate gene expression genome-wide in the intestinal epithelium.

scholarly journals Genome-wide identification of protein binding sites in mammalian cells

2021 ◽  
Author(s):  
Fenglin Liu ◽  
Tianyu Ma ◽  
Yu-Xiang Zhang
Keyword(s):  
Transcription Factors ◽  
Protein Binding ◽  
Protein Interactions ◽  
Binding Sites ◽  
Mammalian Cells ◽  
Protein Binding Sites ◽  
Genome Wide ◽  
Transcription Binding Sites ◽  
Dna Protein Interactions

AbstractWe present GWPBS-Cap, a method to capture genome-wide protein binding sites (PBSs) without using antibodies. Using this technique, we identified many protein binding sites with different binding strengths between proteins and DNA. The PBSs can be useful to predict transcription binding sites and the co-localization of multiple transcription factors in the genome. The results also revealed that active promoters contained more protein binding sites with lower NaCl tolerances. Taken together, GWPBS-Cap can be used to efficiently identify protein binding sites and reveal genome-wide landscape of DNA-protein interactions.

scholarly journals Atlas of Transcription Factor Binding Sites from ENCODE DNase Hypersensitivity Data Across 27 Tissue Types

2018 ◽  
Author(s):  
Cory C. Funk ◽  
Alex M. Casella ◽  
Segun Jung ◽  
Matthew A. Richards ◽  
Alex Rodriguez ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Human Genome ◽  
Binding Sites ◽  
Regulatory Networks ◽  
Specific Binding ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Sequence Motifs ◽  
Link Type ◽  
Genome Wide

AbstractThere is intense interest in mapping the tissue-specific binding sites of transcription factors in the human genome to reconstruct gene regulatory networks and predict functions for non-coding genetic variation. DNase-seq footprinting provides a means to predict genome-wide binding sites for hundreds of transcription factors (TFs) simultaneously. However, despite the public availability of DNase-seq data for hundreds of samples, there is neither a unified analytical workflow nor a publicly accessible database providing the locations of footprints across all available samples. Here, we implemented a workflow for uniform processing of footprints using two state-of-the-art footprinting algorithms: Wellington and HINT. Our workflow scans the footprints generated by these algorithms for 1,530 sequence motifs to predict binding sites for 1,515 human transcription factors. We applied our workflow to detect footprints in 192 DNase-seq experiments from ENCODE spanning 27 human tissues. This collection of footprints describes an expansive landscape of potential TF occupancy. At thresholds optimized through machine learning, we report high-quality footprints covering 9.8% of the human genome. These footprints were enriched for true positive TF binding sites as defined by ChIP-seq peaks, as well as for genetic variants associated with changes in gene expression. Integrating our footprint atlas with summary statistics from genome-wide association studies revealed that risk for neuropsychiatric traits was enriched specifically at highly-scoring footprints in human brain, while risk for immune traits was enriched specifically at highly-scoring footprints in human lymphoblasts. Our cloud-based workflow is available at github.com/globusgenomics/genomics-footprint and a database with all footprints and TF binding site predictions are publicly available at http://data.nemoarchive.org/other/grant/sament/sament/footprint_atlas.

scholarly journals The AP-1 factors FOSL1 and FOSL2 co-regulate human Th17 responses

2021 ◽  
Author(s):  
Ankitha Shetty ◽  
Subhash Kumar Tripathi ◽  
Sini Junttila ◽  
Tanja Buchacher ◽  
Rahul Biradar ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Molecular Networks ◽  
Cell Identity ◽  
Over Expression ◽  
Genome Wide ◽  
Associated Proteins ◽  
Human And Mouse

Th17 cells protect mucosal barriers, but their aberrant activity can cause autoimmunity. Molecular networks dictating human Th17 function are largely unexplored, and this hinders disease-studies. Here, we investigated the functions of the AP-1 proteins FOSL1 and FOSL2 in inducing human Th17 responses. Transient knockdown and over-expression strategies demonstrated the two proteins to inhibit Th17-cell identity, while revealing a novel cooperativity between their functions. Strikingly, FOSL1 plays different roles in human and mouse and FOSL-mediated Th17 regulation is opposed by the AP-1 factor, BATF. Genome-wide occupancy analysis indicated the co-localization of FOSL1, FOSL2 and BATF in the proximity of key Th17 genes. The functional interplay among these transcription factors (TFs) is potentially governed by sharing interactions with a common set of lineage-associated proteins. We further discovered that the genomic binding sites of these factors harbor a large number of disease-linked SNPs, many of which alter the ability of a given factor to bind DNA. Our findings thus provide crucial insights into the pathology of Th17-mediated diseases.

scholarly journals Mechanisms of Binding Specificity among bHLH Transcription Factors

2021 ◽  
Vol 22 (17) ◽  
pp. 9150
Author(s):  
Xabier de Martin ◽  
Reza Sodaei ◽  
Gabriel Santpere
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Nucleosome Occupancy ◽  
Genomic Region ◽  
Post Translational Modifications ◽  
Helix Loop Helix ◽  
Dna Motif ◽  
Genome Wide ◽  
Bhlh Transcription Factors ◽  
Specific Genomic Region

The transcriptome of every cell is orchestrated by the complex network of interaction between transcription factors (TFs) and their binding sites on DNA. Disruption of this network can result in many forms of organism malfunction but also can be the substrate of positive natural selection. However, understanding the specific determinants of each of these individual TF-DNA interactions is a challenging task as it requires integrating the multiple possible mechanisms by which a given TF ends up interacting with a specific genomic region. These mechanisms include DNA motif preferences, which can be determined by nucleotide sequence but also by DNA’s shape; post-translational modifications of the TF, such as phosphorylation; and dimerization partners and co-factors, which can mediate multiple forms of direct or indirect cooperative binding. Binding can also be affected by epigenetic modifications of putative target regions, including DNA methylation and nucleosome occupancy. In this review, we describe how all these mechanisms have a role and crosstalk in one specific family of TFs, the basic helix-loop-helix (bHLH), with a very conserved DNA binding domain and a similar DNA preferred motif, the E-box. Here, we compile and discuss a rich catalog of strategies used by bHLH to acquire TF-specific genome-wide landscapes of binding sites.

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