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Systematic analysis of effects of naturally occurring insertions and deletions that alter transcription factor spacing identifies tolerant and sensitive transcription factor pairs

ABSTRACT: Systematic analysis of effects of naturally occurring insertions and deletions that alter transcription factor spacing identifies tolerant and sensitive transcription factor pairs

PROVIDER: PRJNA737329 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14803556.fastq.gz	Fastqsanger.gz
	SRR14803557.fastq.gz	Fastqsanger.gz
	SRR14803558.fastq.gz	Fastqsanger.gz
	SRR14803559.fastq.gz	Fastqsanger.gz
	SRR14803560.fastq.gz	Fastqsanger.gz

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Systematic analysis of effects of naturally occurring insertions and deletions that alter transcription factor spacing identifies tolerant and sensitive transcription factor pairs [RNA-seq]

Project description:Regulation of gene expression requires the combinatorial binding of sequence-specific transcription factors (TFs) at promoters and enhancers. Prior studies showed that alterations in the spacing between TF binding sites can influence promoter and enhancer activity. However, the relative importance of TF spacing alterations resulting from naturally occurring insertions and deletions (InDels) has not been systematically analyzed. To address this question, we first characterized the genome-wide spacing relationships of 75 TFs in K562 cells as determined by ChIP-sequencing. We found a dominant pattern of a relaxed range of spacing between collaborative factors, including forty-six factors exclusively exhibiting relaxed spacing with their binding partners. Next, we exploited millions of InDels provided by genetically diverse mouse strains and human individuals to investigate the effects of altered spacing on TF binding and local histone acetylation. Spacing alterations resulting from naturally occurring InDels are generally tolerated in comparison to genetic variants directly affecting TF binding sites. A remarkable range of tolerance was further established for PU.1 and C/EBPβ, which exhibit relaxed spacing, by introducing synthetic spacing alterations ranging from 5-bp increase to >30-bp decrease using CRISPR/Cas9 mutagenesis. These findings provide implications for understanding mechanisms underlying enhancer selection and for interpretation of non-coding genetic variation.

2022-01-28 | GSE178079 | GEO

Systematic analysis of effects of naturally occurring insertions and deletions that alter transcription factor spacing identifies tolerant and sensitive transcription factor pairs [ChIP-seq]

2022-01-28 | GSE178078 | GEO

Systematic analysis of effects of naturally occurring insertions and deletions that alter transcription factor spacing identifies tolerant and sensitive transcription factor pairs [ATAC-seq]

2022-01-28 | GSE178077 | GEO

Systematic analysis of naturally occurring insertions and deletions that alter transcription factor spacing identifies tolerant and sensitive transcription factor pairs.

Project description:Regulation of gene expression requires the combinatorial binding of sequence-specific transcription factors (TFs) at promoters and enhancers. Prior studies showed that alterations in the spacing between TF binding sites can influence promoter and enhancer activity. However, the relative importance of TF spacing alterations resulting from naturally occurring insertions and deletions (InDels) has not been systematically analyzed. To address this question, we first characterized the genome-wide spacing relationships of 73 TFs in human K562 cells as determined by ChIP-seq (chromatin immunoprecipitation sequencing). We found a dominant pattern of a relaxed range of spacing between collaborative factors, including 45 TFs exclusively exhibiting relaxed spacing with their binding partners. Next, we exploited millions of InDels provided by genetically diverse mouse strains and human individuals to investigate the effects of altered spacing on TF binding and local histone acetylation. These analyses suggested that spacing alterations resulting from naturally occurring InDels are generally tolerated in comparison to genetic variants directly affecting TF binding sites. To experimentally validate this prediction, we introduced synthetic spacing alterations between PU.1 and C/EBPβ binding sites at six endogenous genomic loci in a macrophage cell line. Remarkably, collaborative binding of PU.1 and C/EBPβ at these locations tolerated changes in spacing ranging from 5 bp increase to >30 bp decrease. Collectively, these findings have implications for understanding mechanisms underlying enhancer selection and for the interpretation of non-coding genetic variation.

| S-EPMC8809895 | biostudies-literature

Systematic analysis of effects of naturally occurring insertions and deletions that alter transcription factor spacing identifies tolerant and sensitive transcription factor pairs [RNA-seq]

Project description:Systematic analysis of effects of naturally occurring insertions and deletions that alter transcription factor spacing identifies tolerant and sensitive transcription factor pairs [RNA-seq]

| PRJNA737333 | ENA

Systematic analysis of effects of naturally occurring insertions and deletions that alter transcription factor spacing identifies tolerant and sensitive transcription factor pairs [ATAC-seq]

| PRJNA737331 | ENA

Systematic analysis of effects of naturally occurring insertions and deletions that alter transcription factor spacing identifies tolerant and sensitive transcription factor pairs [ChIP-seq]

| PRJNA737332 | ENA

Systematic analysis of effects of naturally occurring insertions and deletions that alter transcription factor spacing identifies tolerant and sensitive transcription factor pairs

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

2022-01-28 | GSE178080 | GEO

esBAF chromatin remodeling complexes promote spacing of nucleosomes flanking pluripotency factor binding sites

Project description:We showed that topoisomerase II synergizes with BAF (mSWI/SNF) ATP-dependent chromatin remodeling complexes genome-wide to resolve facultative heterochromatin to accessible chromatin. To study the consequences of this on transcription factors, we performed MNase-seq on light digest of native chromatin in Brg1 conditional knockout embryonic stem (ES) cells. We found that spacing of nucleosomes flanking pluripotency factor binding sites specifically partially collapsed upon Brg1 deletion, indicating that pluripotency factor binding is likely lost.

2017-03-01 | GSE94040 | GEO

Differential Nucleosome Spacing in Neurons and Glia

Project description:Eukaryotic chromosomes are composed of chromatin, in which regularly spaced nucleosomes containing ~147 bp of DNA are separated by linker DNA. Most eukaryotic cells have a characteristic average nucleosome spacing of ~190 bp, corresponding to a ~45 bp linker. However, cortical neurons have a shorter average spacing of ~165 bp. The significance of this atypical global chromatin organization is unclear. We have compared the chromatin structures of purified mouse dorsal root ganglia (DRG) neurons, cortical oligodendrocyte precursor cells (OPCs) and cortical astrocytes. DRG neurons have short average spacing (~165 bp), whereas OPCs (~182 bp) and astrocytes (~183 bp) have longer spacing. We measured nucleosome positions by MNase-seq and gene expression by RNA-seq. Most genes in all three cell types have a promoter chromatin organization typical of active genes: a nucleosome-depleted region at the promoter flanked by regularly spaced nucleosomes phased relative to the transcription start site. In DRG neurons, the spacing of phased nucleosomes downstream of promoters (~178 bp) is longer than expected from the genomic average, whereas phased nucleosome spacing in OPCs and astrocytes is similar to the global average (~183 bp). Thus, the atypical nucleosome spacing of neuronal chromatin does not extend to promoter-proximal regions.

2019-10-07 | GSE133966 | GEO

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