Similar Datasets
Project description:Regulatory elements activate promoters by recruiting transcription factors (TFs) to specific motifs. Notably, TF-DNA interactions often depend on cooperativity with colocalized partners, suggesting an underlying cis-regulatory syntax. To explore TF cooperativity in mammals, we analyze ∼500 mouse and human primary cells by combining an atlas of TF motifs, footprints, ChIP-seq, transcriptomes, and accessibility. We uncover two TF groups that colocalize with most expressed factors, forming stripes in hierarchical clustering maps. The first group includes lineage-determining factors that occupy DNA elements broadly, consistent with their key role in tissue-specific transcription. The second one, dubbed universal stripe factors (USFs), comprises ∼30 SP, KLF, EGR, and ZBTB family members that recognize overlapping GC-rich sequences in all tissues analyzed. Knockouts and single-molecule tracking reveal that USFs impart accessibility to colocalized partners and increase their residence time. Mammalian cells have thus evolved a TF superfamily with overlapping DNA binding that facilitate chromatin accessibility.
| S-EPMC9481673 | biostudies-literature
Project description:"Stripe" transcription factors provide accessibility to co-binding partners in mammalian genomes.
| PRJNA692426 | ENA
Project description:In mammals, transcriptional factors (TFs) drive gene expression by binding to regulatory elements in a cooperative manner. Deciphering the rules of such cooperation is crucial to obtain a full understanding of cellular homeostasis and development. Although this is a long-standing topic, there is no comprehensive database for biologists to access the syntax of TF binding sites. Here we present TFSyntax (https://tfsyntax.zhaopage.com), a database focusing on the arrangement of TF binding sites. TFSyntax maps the binding motif of 1299 human TFs and 890 mouse TFs across 382 cells and tissues, representing the most comprehensive TF binding map to date. In addition to location, TFSyntax defines motif positional preference, density and colocalization within accessible elements. Powered by a series of functional modules based on web interface, users can freely search, browse, analyze, and download data of interest. With comprehensive characterization of TF binding syntax across distinct tissues and cell types, TFSyntax represents a valuable resource and platform for studying the mechanism of transcriptional regulation and exploring how regulatory DNA variants cause disease.
| S-EPMC9825613 | biostudies-literature
Project description:BACKGROUND: The computational prediction of Transcription Factor Binding Sites (TFBS) remains a challenge due to their short length and low information content. Comparative genomics approaches that simultaneously consider several related species and favor sites that have been conserved throughout evolution improve the accuracy (specificity) of the predictions but are limited due to a phenomenon called binding site turnover, where sequence evolution causes one TFBS to replace another in the same region. In parallel to this development, an increasing number of mammalian genomes are now sequenced and it is becoming possible to infer, to a surprisingly high degree of accuracy, ancestral mammalian sequences. RESULTS: We propose a TFBS prediction approach that makes use of the availability of inferred ancestral mammalian genomes to improve its accuracy. This method aims to identify binding loci, which are regions of a few hundred base pairs that have preserved their potential to bind a given transcription factor over evolutionary time. After proposing a neutral evolutionary model of predicted TFBS counts in a DNA region of a given length, we use it to identify regions that have preserved the number of predicted TFBS they contain to an unexpected degree given their divergence. The approach is applied to human chromosome 1 and shows significant gains in accuracy as compared to both existing single-species and multi-species TFBS prediction approaches, in particular for transcription factors that are subject to high turnover rates. AVAILABILITY: The source code and predictions made by the program are available at http://www.cs.mcgill.ca/~blanchem/bindingLoci.
| S-EPMC3526440 | biostudies-literature
Project description:Mammalian genome encodes approximately 1,700 transcription factors (TFs), 1,300 out of which have sequence specific binding motifs. Transcription in mammalian cells is regulated by the recruitment of TFs to specific cis-regulatory elements. In spite of consistent efforts on the function of individual TF, the question still remains how TFs bind to DNA and form enhancer. Here, we try to solve this problem by investigating the relationship between TF binding pattern and chromatin accessibility (ATAC-Seq). We first systematically acquired ATAC-Seq dataset as well as matched RNA-Seq dataset from different mouse primary tissues. A comprehensive TF binding map was built for each tissue/cell type by genomic approaches.
2022-07-21 | GSE165129 | GEO
Project description:Mammalian genome encodes approximately 1,700 transcription factors (TFs), 1,300 out of which have sequence specific binding motifs. Transcription in mammalian cells is regulated by the recruitment of TFs to specific cis-regulatory elements. In spite of consistent efforts on the function of individual TF, the question still remains how TFs bind to DNA and form enhancer. Here, we try to solve this problem by investigating the relationship between TF binding pattern and chromatin accessibility (ATAC-Seq). We first systematically acquired ATAC-Seq dataset as well as matched RNA-Seq dataset from different mouse primary tissues. A comprehensive TF binding map was built for each tissue/cell type by genomic approaches.
2022-07-21 | GSE165128 | GEO
Project description:Mammalian genome encodes approximately 1,700 transcription factors (TFs), 1,300 out of which have sequence specific binding motifs. Transcription in mammalian cells is regulated by the recruitment of TFs to specific cis-regulatory elements. In spite of consistent efforts on the function of individual TF, the question still remains how TFs bind to DNA and form enhancer. Here, we try to solve this problem by investigating the relationship between TF binding pattern and chromatin accessibility (ATAC-Seq). We first systematically acquired ATAC-Seq dataset as well as matched RNA-Seq dataset from different mouse primary tissues. A comprehensive TF binding map was built for each tissue/cell type by genomic approaches.
2022-07-21 | GSE184596 | GEO
Project description:Chromatin remodelling complexes evict, slide, insert or replace nucleosomes, which represent an intrinsic barrier for access to DNA. These remodellers function in most aspects of genome utilization including transcription-factor binding, DNA replication and repair1,2. Although they are frequently mutated in cancer3, it remains largely unclear how the four mammalian remodeller families (SWI/SNF, ISWI, CHD and INO80) orchestrate the global organization of nucleosomes. Here we generated viable embryonic stem cells that lack SNF2H, the ATPase of ISWI complexes, enabling study of SNF2H cellular function, and contrast it to BRG1, the ATPase of SWI/SNF. Loss of SNF2H decreases nucleosomal phasing and increases linker lengths, providing in vivo evidence for an ISWI function in ruling nucleosomal spacing in mammals. Systematic analysis of transcription-factor binding reveals that these remodelling activities have specific effects on binding of different transcription factors. One group critically depends on BRG1 and contains the transcriptional repressor REST, whereas a non-overlapping set of transcription factors, including the insulator protein CTCF, relies on SNF2H. This selectivity readily explains why chromosomal folding and insulation of topologically associated domains requires SNF2H, but not BRG1. Collectively, this study shows that mammalian ISWI is critical for nucleosomal periodicity and nuclear organization and that transcription factors rely on specific remodelling pathways for correct genomic binding.
| S-EPMC6522387 | biostudies-literature
Project description:Ligand-dependent transcription by the nuclear receptor glucocorticoid receptor (GR) is mediated by interactions with coregulators. The role of these interactions in determining selective binding of GR to regulatory elements remains unclear. Recent findings indicate that a large fraction of genomic GR binding coincides with chromatin that is accessible prior to hormone treatment, suggesting that receptor binding is dictated by proteins that maintain chromatin in an open state. Combining DNaseI accessibility and chromatin immunoprecipitation with high-throughput sequencing, we identify the activator protein 1 (AP1) as a major partner for productive GR-chromatin interactions. AP1 is critical for GR-regulated transcription and recruitment to co-occupied regulatory elements, illustrating an extensive AP1-GR interaction network. Importantly, the maintenance of baseline chromatin accessibility facilitates GR recruitment and is dependent on AP1 binding. We propose a model in which the basal occupancy of transcription factors acts to prime chromatin and direct inducible transcription factors to select regions in the genome.
| S-EPMC3138120 | biostudies-literature
Project description:The X and Y sex chromosomes of placental mammals show hallmarks of a tumultuous evolutionary past. The X Chromosome has a rich and conserved gene content, while the Y Chromosome has lost most of its genes. In the Transcaucasian mole vole Ellobius lutescens, the Y Chromosome including Sry has been lost, and both females and males have a 17,X diploid karyotype. Similarly, the closely related Ellobius talpinus, has a 54,XX karyotype in both females and males. Here, we report the sequencing and assembly of the E. lutescens and E. talpinus genomes. The results indicate that the loss of the Y Chromosome in E. lutescens and E. talpinus occurred in two independent events. Four functional homologs of mouse Y-Chromosomal genes were detected in both female and male E. lutescens, of which three were also detected in the E. talpinus genome. One of these is Eif2s3y, known as the only Y-derived gene that is crucial for successful male meiosis. Female and male E. lutescens can carry one and the same X Chromosome with a largely conserved gene content, including all genes known to function in X Chromosome inactivation. The availability of the genomes of these mole vole species provides unique models to study the dynamics of sex chromosome evolution.
| S-EPMC5052041 | biostudies-literature