Pioneer factor Pax7 deploys a stable enhancer repertoire for specification of cell fate
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA343791 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Deployment of a cell-specifying enhancer repertoire by the pioneer factor Pax7 The establishment and maintenance of cell identity depends on implementation of stable cell-specific chromatin landscapes. Pioneer transcription factors establish new cell fate competences by triggering chromatin remodeling during development. Here, we used pituitary cell specification to define the salient features of pioneer action. Comparison of purified pituitary cells of different lineages showed that chromatin accessibility differs at enhancers rather than promoters. The pioneer factor Pax7 specifies one pituitary lineage identity by opening a specific repertoire of enhancers that are distinct from the myogenic targets of Pax7. Pax7 binds its pioneer targets rapidly and days before chromatin remodeling and gene activation. Finally, enhancers opened by Pax7-dependent chromatin remodeling exhibit loss of DNA methylation and they acquire long term epigenetic memory. The present work identifies enhancer pioneering as a critical feature for cell fate specification and maintenance.
2018-01-24 | GSE87181 | GEO
Project description:Deployment of a cell-specifying enhancer repertoire by the pioneer factor Pax7 The establishment and maintenance of cell identity depends on implementation of stable cell-specific chromatin landscapes. Pioneer transcription factors establish new cell fate competences by triggering chromatin remodeling during development. Here, we used pituitary cell specification to define the salient features of pioneer action. Comparison of purified pituitary cells of different lineages showed that chromatin accessibility differs at enhancers rather than promoters. The pioneer factor Pax7 specifies one pituitary lineage identity by opening a specific repertoire of enhancers that are distinct from the myogenic targets of Pax7. Pax7 binds its pioneer targets rapidly and days before chromatin remodeling and gene activation. Finally, enhancers opened by Pax7-dependent chromatin remodeling exhibit loss of DNA methylation and they acquire long term epigenetic memory. The present work identifies enhancer pioneering as a critical feature for cell fate specification and maintenance.
2018-01-24 | GSE87180 | GEO
Project description:Deployment of a cell-specifying enhancer repertoire by the pioneer factor Pax7 The establishment and maintenance of cell identity depends on implementation of stable cell-specific chromatin landscapes. Pioneer transcription factors establish new cell fate competences by triggering chromatin remodeling during development. Here, we used pituitary cell specification to define the salient features of pioneer action. Comparison of purified pituitary cells of different lineages showed that chromatin accessibility differs at enhancers rather than promoters. The pioneer factor Pax7 specifies one pituitary lineage identity by opening a specific repertoire of enhancers that are distinct from the myogenic targets of Pax7. Pax7 binds its pioneer targets rapidly and days before chromatin remodeling and gene activation. Finally, enhancers opened by Pax7-dependent chromatin remodeling exhibit loss of DNA methylation and they acquire long term epigenetic memory. The present work identifies enhancer pioneering as a critical feature for cell fate specification and maintenance.
2018-01-24 | GSE87178 | GEO
Project description:Deployment of a cell-specifying enhancer repertoire by the pioneer factor Pax7 The establishment and maintenance of cell identity depends on implementation of stable cell-specific chromatin landscapes. Pioneer transcription factors establish new cell fate competences by triggering chromatin remodeling during development. Here, we used pituitary cell specification to define the salient features of pioneer action. Comparison of purified pituitary cells of different lineages showed that chromatin accessibility differs at enhancers rather than promoters. The pioneer factor Pax7 specifies one pituitary lineage identity by opening a specific repertoire of enhancers that are distinct from the myogenic targets of Pax7. Pax7 binds its pioneer targets rapidly and days before chromatin remodeling and gene activation. Finally, enhancers opened by Pax7-dependent chromatin remodeling exhibit loss of DNA methylation and they acquire long term epigenetic memory. The present work identifies enhancer pioneering as a critical feature for cell fate specification and maintenance.
2018-01-24 | GSE87184 | GEO
Project description:Deployment of a cell-specifying enhancer repertoire by the pioneer factor Pax7 The establishment and maintenance of cell identity depends on implementation of stable cell-specific chromatin landscapes. Pioneer transcription factors establish new cell fate competences by triggering chromatin remodeling during development. Here, we used pituitary cell specification to define the salient features of pioneer action. Comparison of purified pituitary cells of different lineages showed that chromatin accessibility differs at enhancers rather than promoters. The pioneer factor Pax7 specifies one pituitary lineage identity by opening a specific repertoire of enhancers that are distinct from the myogenic targets of Pax7. Pax7 binds its pioneer targets rapidly and days before chromatin remodeling and gene activation. Finally, enhancers opened by Pax7-dependent chromatin remodeling exhibit loss of DNA methylation and they acquire long term epigenetic memory. The present work identifies enhancer pioneering as a critical feature for cell fate specification and maintenance.
2018-01-24 | GSE87183 | GEO
Project description:Deployment of a cell-specifying enhancer repertoire by the pioneer factor Pax7 The establishment and maintenance of cell identity depends on implementation of stable cell-specific chromatin landscapes. Pioneer transcription factors establish new cell fate competences by triggering chromatin remodeling during development. Here, we used pituitary cell specification to define the salient features of pioneer action. Comparison of purified pituitary cells of different lineages showed that chromatin accessibility differs at enhancers rather than promoters. The pioneer factor Pax7 specifies one pituitary lineage identity by opening a specific repertoire of enhancers that are distinct from the myogenic targets of Pax7. Pax7 binds its pioneer targets rapidly and days before chromatin remodeling and gene activation. Finally, enhancers opened by Pax7-dependent chromatin remodeling exhibit loss of DNA methylation and they acquire long term epigenetic memory. The present work identifies enhancer pioneering as a critical feature for cell fate specification and maintenance.
2018-01-24 | GSE87179 | GEO
Project description:The pioneer transcription factor Pax7 contains two DNA binding domains (DBD), a paired and a homeo domain. Previous work on Pax7 and the related Pax3 showed that each DBD binds a cognate DNA sequence, thus defining two targets of binding and possibly modalities of action. Genomic targets of Pax7 pioneer action leading to chromatin opening are enriched for composite DNA target sites containing juxtaposed sites for both paired and homeo domains. The present work investigated the implication of the DBDs in pioneer action. We show that the composite sequence is a higher affinity binding site and that efficient binding to this site involves both DBDs of the same Pax7 molecule. This binding is not sensitive to cytosine methylation of the DNA sites consistent with pioneer action within nucleosomal heterochromatin. Introduction of single amino acid mutations in either paired or homeo domain that impair binding to cognate DNA sequences showed that both DBDs must be intact for pioneer action. In contrast, only the paired domain is required for low affinity binding of heterochromatin sites. Thus, Pax7 pioneer action on heterochromatin requires unique protein:DNA interactions that are more complex compared to its simpler DNA binding modalities at accessible enhancer target sites.
2021-07-28 | GSE173740 | GEO
Project description:The pioneer transcription factor Pax7 contains two DNA binding domains (DBD), a paired and a homeo domain. Previous work on Pax7 and the related Pax3 showed that each DBD binds a cognate DNA sequence, thus defining two targets of binding and possibly modalities of action. Genomic targets of Pax7 pioneer action leading to chromatin opening are enriched for composite DNA target sites containing juxtaposed sites for both paired and homeo domains. The present work investigated the implication of the DBDs in pioneer action. We show that the composite sequence is a higher affinity binding site and that efficient binding to this site involves both DBDs of the same Pax7 molecule. This binding is not sensitive to cytosine methylation of the DNA sites consistent with pioneer action within nucleosomal heterochromatin. Introduction of single amino acid mutations in either paired or homeo domain that impair binding to cognate DNA sequences showed that both DBDs must be intact for pioneer action. In contrast, only the paired domain is required for low affinity binding of heterochromatin sites. Thus, Pax7 pioneer action on heterochromatin requires unique protein:DNA interactions that are more complex compared to its simpler DNA binding modalities at accessible enhancer target sites.
2021-07-28 | GSE173741 | GEO
Project description:The pioneer transcription factor Pax7 contains two DNA binding domains (DBD), a paired and a homeo domain. Previous work on Pax7 and the related Pax3 showed that each DBD binds a cognate DNA sequence, thus defining two targets of binding and possibly modalities of action. Genomic targets of Pax7 pioneer action leading to chromatin opening are enriched for composite DNA target sites containing juxtaposed sites for both paired and homeo domains. The present work investigated the implication of the DBDs in pioneer action. We show that the composite sequence is a higher affinity binding site and that efficient binding to this site involves both DBDs of the same Pax7 molecule. This binding is not sensitive to cytosine methylation of the DNA sites consistent with pioneer action within nucleosomal heterochromatin. Introduction of single amino acid mutations in either paired or homeo domain that impair binding to cognate DNA sequences showed that both DBDs must be intact for pioneer action. In contrast, only the paired domain is required for low affinity binding of heterochromatin sites. Thus, Pax7 pioneer action on heterochromatin requires unique protein:DNA interactions that are more complex compared to its simpler DNA binding modalities at accessible enhancer target sites.
2021-07-28 | GSE173742 | GEO
Project description:Pioneer factors are transcription factors (TFs) that have the unique ability to recognise their target DNA sequences within closed chromatin. Whereas their interactions with cognate DNA is similar to other TFs, their ability to interact with chromatin remains poorly understood. Having previously defined the modalities of DNA interactions for the pioneer factor Pax7, we have now used natural isoforms of this pioneer as well as deletion and replacement mutants to investigate the Pax7 structural requirements for chromatin interaction and opening. We show that the GL+ natural isoform of Pax7 that has two extra amino acids within the DNA binding paired domain is unable to activate the melanotrope transcriptome and to fully activate a large subset of melanotrope-specific enhancers targeted for Pax7 pioneer action. This enhancer subset remains in the primed state rather than being fully activated, despite the GL+ isoform having similar intrinsic transcriptional activity as the GL- isoform. C-terminal deletions of Pax7 lead to the same loss of pioneer ability, with similar reduced recruitments of the cooperating TF Tpit and of the co-regulators Ash2 and BRG1. This suggest complex interrelations between the DNA binding and C-terminal domains of Pax7 that are crucial for its chromatin opening pioneer ability.
2023-06-17 | GSE225227 | GEO