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Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1 [ChIP-ISO]

ABSTRACT: Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1 [ChIP-ISO]

PROVIDER: PRJNA1037507 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26779749_1.fastq.gz	Fastqsanger.gz
	SRR26779749_2.fastq.gz	Fastqsanger.gz
	SRR26779750_1.fastq.gz	Fastqsanger.gz
	SRR26779750_2.fastq.gz	Fastqsanger.gz
	SRR26779751_1.fastq.gz	Fastqsanger.gz

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Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1 [ChIP-ISO]

Project description:Pioneer factors (PFs) are a subset of transcription factors (TFs) that can bind to nucleosomal DNA and invade closed chromatin. Despite that nucleosomes do not present a strong barrier to PF binding, PF can only bind to a small fraction of motifs in the genome. The underlying mechanism of such binding selectivity is not well understood. Here, we design a high-throughput assay named Chromatin Immunoprecipitation over Integrated Synthetic Oligonucleotides (ChIP-ISO) to systematically dissect the sequence features affecting the binding specificity of a classic PF, FOXA1, in A549 human lung carcinoma cells. This method involves integrating thousands of synthetic sequences containing FOXA1 motifs into a fixed genomic locus, followed by FOXA1 chromatin immunoprecipitation (ChIP) and amplicon sequencing. We find that 1) FOXA1 binding is affected by motif strength and co-binding TFs AP-1 and CEBPB, with AP-1 playing a major role in promoting FOXA1 binding, 2) FOXA1 binding in vivo and in vitro are poorly correlated, and FOXA1 and AP-1 show binding cooperativity in vitro, 3) FoxA1’s binding specificity is mostly determined by the local sequences, whereas chromatin context, including heterochromatin marks, only plays a minor role, and 4) AP-1 is at least partially responsible for differential binding of FOXA1 in different cell types. Finally, neural network analysis shows that AP-1 and CEBPB motifs are predictive of FOXA1 ChIP-seq peaks in A549, but not in some other cell types. In summary, combining ChIP-ISO with in vitro and in silico analyses, our study provides insights into the genetic rules underlying PF binding specificity and reveals a mechanism for its regulation during cell differentiation.

2023-11-09 | GSE247411 | GEO

Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1 [EMSA-seq]

2023-11-09 | GSE247431 | GEO

Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1 [RNA-seq]

2023-11-09 | GSE247414 | GEO

Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1 [ChIP-seq]

2023-11-09 | GSE247412 | GEO

Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1

Project description:Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1

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Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1 [RNA-seq]

Project description:Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1 [RNA-seq]

| PRJNA1037515 | ENA

Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1 [EMSA-seq]

Project description:Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1 [EMSA-seq]

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Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1 [ChIP-seq]

Project description:Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1 [ChIP-seq]

| PRJNA1037508 | ENA

Binding of the pioneer factor FOXA1 is independent of hormonal signalling

Project description:We hormone deprived MCF-7 and ZR75-1 breast cancer cells for three days and treated them with vehicle (ethanol) or estrogen for 45 minutes. We then performed FOXA1 ChIP-seq and showed that the vast majority (>99%) of FOXA1 binding events are not affected by steroid conditions. A small number (<1%) of FOXA1 binding sites appear to be induced by estrogen, but these are not genuine de novo binding sites and represent ‘shadow’ binding sites that result from chromatin interactions at super-enhancer containing estrogen-regulated genomic regions. FOXA1 is therefore not regulated by estrogen and remains a bone fide therapeutic target that is entirely upstream of the ER complex.

2019-03-07 | GSE112969 | GEO

Genome-wide analysis reveals positional-nucleosome-oriented binding pattern of pioneer factor FOXA1

Project description:By analysis of ChIP-exo of FOXA1 in LNCaP, we find that an astonishing genome-wide "well-positioned" configuration prevalently occurs between FOXA1 motif and the dyad of nucleosome. Here we performed ChIP-seq data of eight chromatin remodelers and found a higher occupancy of these remodelers on these well-positioned FOXA1 motif sites. Together, our results support a positional-nucleosome-oriented accessing model, in which FOXA1 can examine each underlying DNA nucleotide and be able to sense all potential motifs regardless if they face inward or outward to histone octamers along the DNA helix axis. We have performed ChIP-seq of eight chromatin remodeler factors.

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