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Genome-wide binding reveals intrinsic specificity and regulatory function of lineage-specifying bHLH transcription factors

ABSTRACT: Genome-wide binding reveals intrinsic specificity and regulatory function of lineage-specifying bHLH transcription factors

PROVIDER: PRJNA382708 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5445220.fastq.gz	Fastqsanger.gz
	SRR5445230.fastq.gz	Fastqsanger.gz
	SRR5445240.fastq.gz	Fastqsanger.gz
	SRR5445250.fastq.gz	Fastqsanger.gz
	SRR5445221.fastq.gz	Fastqsanger.gz

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Genome-wide binding reveals intrinsic specificity and regulatory function of lineage-specifying bHLH transcription factors (ATAC-Seq).

Project description:Developmental mechanisms of lineage specification are crucial to tissue-specific gene regulation, and crucial lineage-specification factors are associated with developmental and oncogenic diseases. The mechanisms by which these factors regulate their distinct transcriptional profiles remains unclear. Comparison of their binding in a common context reveals that such specificity is intrinsic to these factors, and not simply a consequence of distinction in preference for, or availability of accessible chromatin at their respective binding sites.

2018-02-27 | GSE97714 | GEO

Genome-wide binding reveals intrinsic specificity and regulatory function of lineage-specifying bHLH transcription factors (RNA-Seq).

2018-02-27 | GSE97713 | GEO

Genome-wide binding reveals intrinsic specificity and regulatory function of lineage-specifying bHLH transcription factors (ChIP-Seq).

2018-02-27 | GSE97712 | GEO

Genome-wide binding reveals intrinsic specificity and regulatory function of lineage-specifying bHLH transcription factors

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-02-27 | GSE97715 | GEO

Genomic regions flanking E-box sites influence DNA binding specificity of bHLH transcription factors through DNA shape (validation)

2013-03-29 | GSE44437 | GEO

Genomic regions flanking E-box sites influence DNA binding specificity of bHLH transcription factors through DNA shape (validation)

Project description:DNA sequence is a major determinant of the binding specificity of transcription factors (TFs) for their genomic targets. However, eukaryotic cells often express, at the same time, TFs with highly similar DNA binding motifs but distinct in vivo targets. Currently, it is not well understood how TFs with seemingly identical DNA motifs achieve unique specificities in vivo. Here, we used custom protein binding microarrays to analyze TF specificity for putative binding sites in their genomic sequence context. Using yeast TFs Cbf1 and Tye7 as our case study, we found that binding sites of these bHLH TFs (i.e., E-boxes) are bound differently in vitro and in vivo, depending on their genomic context. Computational analyses suggest that nucleotides outside E-box binding sites contribute to specificity by influencing the 3D structure of DNA binding sites. Thus, local shape of target sites might play a widespread role in achieving regulatory specificity within TF families. Two protein binding microarray (PBM) experiments of Saccharomyces cerevisiae transcription factors were performed. Briefly, the PBMs involved binding GST-tagged yeast transcription factors Cbf1 and Tye7 to double-stranded 44K Agilent microarrays in order to determine the accuracy of our regression models for TF-DNA binding specificity. Briefly, this array contains 30-bp genomic sequences from our initial custom array (Gordan et al 2013, submitted), with 0 through 4 mutations designed at various positions in the genomic sequences. Each sequence in represented in 6 replicate spots. We report the PBM signal intensity for each spot. The PBM protocol is described in Berger et al., Nature Biotechnology 2006 (PMID 16998473).

2013-03-29 | E-GEOD-44437 | biostudies-arrayexpress

Genomic regions flanking E-box sites influence DNA binding specificity of bHLH transcription factors through DNA shape (different concentrations)

2013-03-29 | GSE44436 | GEO

Homotypic cooperativity and collective binding are determinants of bHLH specificity and function

Project description:Eukaryotic cells express transcription factor (TF) paralogues that bind to nearly identical DNA sequences in vitro but bind at different genomic loci and perform different functions in vivo. Predicting how 2 paralogous TFs bind in vivo using DNA sequence alone is an important open problem. Here, we analyzed 2 yeast bHLH TFs, Cbf1p and Tye7p, which have highly similar binding preferences in vitro, yet bind at almost completely non-overlapping target loci in vivo. We dissected the determinants of specificity for these 2 proteins by making a number of chimeric TFs in which we swapped different domains of Cbf1p and Tye7p and determined the effects on in vivo binding and cellular function. From these experiments, we learned that the Cbf1p dimer achieves its specificity by binding cooperatively with other Cbf1p dimers bound nearby. In contrast, we found that Tye7p achieves its specificity by binding cooperatively with three other DNA-binding proteins, Gcr1p, Gcr2p, and Rap1p. Remarkably, most promoters (63%) that are bound by Tye7p do not contain a consensus Tye7p binding site. Using this information, we were able to build simple models to accurately discriminate bound and unbound genomic loci for both Cbf1p and Tye7p. We then successfully reprogrammed the human bHLH NPAS2 to bind Cbf1p in vivo targets and a Tye7p target intergenic region to be bound by Cbf1p. These results demonstrate that the genome-wide binding targets of paralogous TFs can be discriminated using sequence information, and provide lessons about TF specificity that can be applied across the phylogenetic tree.

2019-07-18 | GSE134427 | GEO

Intrinsic DNA binding properties demonstrated for lineage-specifying basic helix-loop-helix transcription factors.

Project description:During development, transcription factors select distinct gene programs, providing the necessary regulatory complexity for temporal and tissue-specific gene expression. How related factors retain specificity, especially when they recognize the same DNA motifs, is not understood. We address this paradox using basic helix-loop-helix (bHLH) transcription factors ASCL1, ASCL2, and MYOD1, crucial mediators of lineage specification. In vivo, these factors recognize the same DNA motifs, yet bind largely different genomic sites and regulate distinct transcriptional programs. This suggests that their ability to identify regulatory targets is defined either by the cellular environment of the partially defined lineages in which they are endogenously expressed, or by intrinsic properties of the factors themselves. To distinguish between these mechanisms, we directly compared the chromatin binding properties of this subset of bHLH factors when ectopically expressed in embryonic stem cells, presenting them with a common chromatin landscape and cellular components. We find that these factors retain distinct binding sites; thus, specificity of binding is an intrinsic property not requiring a restricted landscape or lineage-specific cofactors. Although the ASCL factors and MYOD1 have some distinct DNA motif preference, it is not sufficient to explain the extent of the differential binding. All three factors can bind inaccessible chromatin and induce changes in chromatin accessibility and H3K27ac. A reiterated pattern of DNA binding motifs is uniquely enriched in inaccessible chromatin at sites bound by these bHLH factors. These combined properties define a subclass of lineage-specific bHLH factors and provide context for their central roles in development and disease.

| S-EPMC5880239 | biostudies-literature

Homotypic cooperativity and collective binding are determinants of bHLH specificity and function

Project description:Homotypic cooperativity and collective binding are determinants of bHLH specificity and function

| PRJNA555089 | ENA