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ABSTRACT:
PROVIDER: PRJEB67921 | ENA |
REPOSITORIES: ENA
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Project description:The nucleosome is a fundamental unit of chromatin in eukaryotes, and generally prevents the binding of transcription factors to genomic DNA. Pioneer transcription factors overcome the nucleosome barrier, and bind their target DNA sequences in chromatin. OCT4 is a representative pioneer transcription factor that plays a role in stem cell pluripotency. In the present study, we biochemically analyzed the nucleosome binding by OCT4. Crosslinking mass spectrometry showed that OCT4 binds the nucleosome.
2020-05-13 | PXD019160 | JPOST Repository
Project description:Though the in vitro structural and in vivo spatial characteristics of transcription factor (TF) binding are well defined, TF interactions with chromatin and other companion TFs during development are poorly understood. To analyze such interactions in vivo, we profiled several TFs across a time course of human embryonic stem cell differentiation via CUT&RUN epigenome profiling, and studied their interactions with nucleosomes and co-occurring TFs by Enhanced Chromatin Occupancy (EChO), a computational strategy for classifying TF binding characteristics across time and space. EChO shows that at different enhancer targets, the same TF can employ either direct DNA binding, or “pioneer” nucleosome binding to access them. Pioneer binding is correlated with local binding of other TFs and enhancer motif character, including degeneracy at key bases in the pioneer factor target motif. Our strategy reveals a dynamic exchange of TFs at enhancers across developmental time that is aided by pioneer nucleosome binding.
2019-06-25 | GSE128499 | GEO
Project description:Previous unbiased screening for the nucleosome binding affinity of transcription factors predicts that POU domain transcription factors have strong nucleosome binding potential. Here using reprogramming strategy we found that POU4F3 has pioneer factor activity at ATOH1 target elements that require POU4F3 for their accessibility.
2021-07-09 | GSE150279 | GEO
Project description:BAF complex is one major group of chromatin remodeling factors in mammals. However, how BAF regulated nucleosomes and other histone modifications is not clear. Here we delete BAF250a, a major component in esBAF to study the nucleosome and histone changes in ESCs. We find that deletion of BAF250a leads to nucleosome occupancy increase in TSS regions and non-pioneer transcription factor binding sites. BAF250a deletion also cause overall decrease of H3K27me3 modification. Collectively, these results reveals how BAF complex coordinates nucleosome, histone modification to control ESC function. Sample 1-4: Nucleosome profiles in WT and BAF250a KO ESCs. Sample 5-10: profiling of H3K4me3 and H3K27me3 in WT and BAF250 KO ESCs.
2015-08-03 | E-GEOD-59082 | biostudies-arrayexpress
Project description:Pioneer transcription factors target compact, transcriptionally silent chromatin, thereby enabling gene activation in development, regeneration, and cell reprogramming. However, silent chromatin is heterogenous, varying in nucleosome mobility, nucleosome compaction, and repressive histone modifications, and how pioneer factors may overcome these different chromatin barriers is unknown. We systematically compared the chromatin targeting of 13 embryonic transcription factors and found that the DNA binding domain (DBD) type predicts whether a pioneer factor targets low-turnover nucleosomes in compact chromatin, dynamic nucleosomes in compact chromatin, or function as non-pioneer factors targeting accessible chromatin. By contrast, non-DBD domains enable targeting of repressed chromatin marked by H3K9me3 or H3K27me3. Fusions of different non-DBD segments of heterochromatin-targeting pioneer factors onto SOX2 can expand binding of Sox2 target motifs, including within heterochromatin, and improve cellular reprogramming. Our study unveils how different forms of silent chromatin are coordinately targeted by lineage-specifying factors.
2025-12-03 | GSE299017 | GEO
Project description:Nucleosome-mediated competition of pioneer transcription factors
| PRJNA891341 | ENA
Project description:LFY is pioneer transcription factor
| PRJNA594407 | ENA
Project description:Pioneer transcription factors, by interacting with nucleosomes, scan silent, compact chromatin to target regulatory sequences, enabling cooperative binding events that modulate local chromatin structure and gene activity. However, not all cognate motifs are targeted by pioneer factors and dynamic scanning parameters required to scan compact chromatin are unknown. A combined genomics and single-molecule tracking approach shows that to target DNase-resistant, low-histone turnover sites, pioneer factors FOXA1 and SOX2 display opposite dynamics of chromatin scanning: slow, with low nucleoplasmic diffusion and stable interactions, versus fast, with high nucleoplasmic diffusion and transient interactions, respectively. Despite such differences, the ability of FOXA1 and SOX2 to scan low-mobility chromatin, mediated by protein domains outside of the respective DNA binding domains, leads to targeting silent chromatin. By contrast, non-pioneer HNF4A predominantly targets DNase-sensitive, nucleosome-depleted regions. We conclude that the targeting of compact chromatin sites by pioneer factors can be performed through diverse dynamic processes. Micrococcol nuclease digestion and sequencing (MNase-seq) of human BJ fibroblasts
2023-06-07 | GSE220569 | GEO
Project description:Gene network transitions in embryos and fate-changing contexts involve combinations of transcription factors. A subset of fate-changing transcription factors act as pioneers; they scan and target nucleosomal DNA and initiate cooperative events that can open the local chromatin. But a gap has remained in understanding how molecular interactions with the nucleosome, beyond interactions with the DNA helix, contribute to the chromatin opening phenomenon. Here we identified a short alpha-helical region, conserved among FoxA pioneer factors and separated from the DNA binding domain, that interacts with core histones and is necessary for chromatin opening in vitro. The same domain is necessary for chromatin opening in early mouse embryos and for normal embryonic development and viability. Thus, local opening of chromatin by interactions between pioneer factors and core histones is crucial for genetic programming.
2020-01-22 | GSE134464 | GEO