Specificity in clustering of gene-specific transcription factors is encoded in the genome
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| Title: | Specificity in clustering of gene-specific transcription factors is encoded in the genome |
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| Authors: | Shivali Dongre, Nadine L Vastenhouw |
| Source: | Nucleic Acids Res Nucleic acids research, vol. 53, no. 13 |
| Publisher Information: | Oxford University Press (OUP), 2025. |
| Publication Year: | 2025 |
| Subject Terms: | Gene regulation, Chromatin and Epigenetics, Animals, Zebrafish/genetics, Zebrafish/embryology, Zebrafish/metabolism, Transcription Factors/genetics, Transcription Factors/metabolism, Transcription Factors/chemistry, Zebrafish Proteins/genetics, Zebrafish Proteins/metabolism, Zebrafish Proteins/chemistry, Genome, Multigene Family, Octamer Transcription Factor-3/genetics, Octamer Transcription Factor-3/metabolism, Octamer Transcription Factor-3/chemistry, Nanog Homeobox Protein/genetics, Nanog Homeobox Protein/metabolism, Intrinsically Disordered Proteins/metabolism, Intrinsically Disordered Proteins/genetics, DNA/metabolism, Embryo, Nonmammalian/metabolism |
| Description: | Gene-specific transcription factors (TFs) often form clusters in the nucleus. Such clusters can facilitate transcription, but it remains unclear how they form. It has been suggested that clusters are seeded by the sequence-specific binding of TFs to DNA and grow by interactions between intrinsically disordered regions (IDRs) that bring in more TFs. In this model, specificity in TF clustering must be provided by the IDRs. To investigate this model, we studied TF clustering by quantitative imaging of Nanog, Pou5f3, and Sox19b in zebrafish embryos. Using mutant TFs, we show that the formation of a TF cluster requires the DNA-binding domain (DBD) as well as at least one of its IDRs. Importantly, IDRs are not sufficient to join a pre-existing cluster. Rather, both IDR and DBD are needed. Finally, using chimeric TFs, we show that while IDRs are required to join a cluster, they are quite promiscuous, and it is the DBD that provides specificity to the clustering of a TF. Thus, for any TF to join a cluster, motif recognition is required, which explains the specificity in TF cluster formation. Taken together, our work provides an alternative model for how specificity is achieved in the organization of transcriptional machinery in the nucleus. |
| Document Type: | Article Other literature type |
| File Description: | application/pdf |
| Language: | English |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkaf625 |
| Access URL: | https://serval.unil.ch/notice/serval:BIB_4CD68E481E64 http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_4CD68E481E641 https://serval.unil.ch/resource/serval:BIB_4CD68E481E64.P001/REF.pdf |
| Rights: | CC BY URL: http://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Accession Number: | edsair.doi.dedup.....05668d9dcd0c1cb9ac928aa122d65cf9 |
| Database: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstract: | Gene-specific transcription factors (TFs) often form clusters in the nucleus. Such clusters can facilitate transcription, but it remains unclear how they form. It has been suggested that clusters are seeded by the sequence-specific binding of TFs to DNA and grow by interactions between intrinsically disordered regions (IDRs) that bring in more TFs. In this model, specificity in TF clustering must be provided by the IDRs. To investigate this model, we studied TF clustering by quantitative imaging of Nanog, Pou5f3, and Sox19b in zebrafish embryos. Using mutant TFs, we show that the formation of a TF cluster requires the DNA-binding domain (DBD) as well as at least one of its IDRs. Importantly, IDRs are not sufficient to join a pre-existing cluster. Rather, both IDR and DBD are needed. Finally, using chimeric TFs, we show that while IDRs are required to join a cluster, they are quite promiscuous, and it is the DBD that provides specificity to the clustering of a TF. Thus, for any TF to join a cluster, motif recognition is required, which explains the specificity in TF cluster formation. Taken together, our work provides an alternative model for how specificity is achieved in the organization of transcriptional machinery in the nucleus. |
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| ISSN: | 13624962 03051048 |
| DOI: | 10.1093/nar/gkaf625 |