Nonreciprocal and Conditional Cooperativity Directs the Pioneer Activity of Pluripotency Transcription Factors
Summary: Cooperative binding of transcription factors (TFs) to chromatin orchestrates gene expression programming and cell fate specification. However, the biophysical principles of TF cooperativity remain incompletely understood. Here we use single-molecule fluorescence microscopy to study the part...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-09-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719310198 |
| _version_ | 1819289236824653824 |
|---|---|
| author | Sai Li Eric Bo Zheng Li Zhao Shixin Liu |
| author_facet | Sai Li Eric Bo Zheng Li Zhao Shixin Liu |
| author_sort | Sai Li |
| collection | DOAJ |
| description | Summary: Cooperative binding of transcription factors (TFs) to chromatin orchestrates gene expression programming and cell fate specification. However, the biophysical principles of TF cooperativity remain incompletely understood. Here we use single-molecule fluorescence microscopy to study the partnership between Sox2 and Oct4, two core members of the pluripotency gene regulatory network. We find that the ability of Sox2 to target DNA inside nucleosomes is strongly affected by the translational and rotational positioning of its binding motif. In contrast, Oct4 can access nucleosomal sites with equal capacities. Furthermore, the Sox2-Oct4 pair displays nonreciprocal cooperativity, with Oct4 modulating interaction of Sox2 with the nucleosome but not vice versa. Such cooperativity is conditional upon the composite motif’s residing at specific nucleosomal locations. These results reveal that pioneer factors possess distinct chromatin-binding properties and suggest that the same set of TFs can differentially regulate gene activities on the basis of their motif positions in the nucleosomal context. : Using single-molecule fluorescence imaging, Li et al. investigate the pioneer activities of pluripotency factors Sox2 and Oct4 and find that they exhibit distinct nucleosome binding preferences as well as context-dependent cooperativity, which potentially allows gene-specific transcriptional regulation. Keywords: Sox2, Oct4, nucleosome, single-molecule fluorescence, pioneer activity, transcription factor, cooperative binding, gene regulatory network |
| first_indexed | 2024-12-24T03:03:39Z |
| format | Article |
| id | doaj.art-01e45d584b60408782f54b7bb223162d |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-24T03:03:39Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-01e45d584b60408782f54b7bb223162d2022-12-21T17:18:05ZengElsevierCell Reports2211-12472019-09-01281026892703.e4Nonreciprocal and Conditional Cooperativity Directs the Pioneer Activity of Pluripotency Transcription FactorsSai Li0Eric Bo Zheng1Li Zhao2Shixin Liu3Laboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, NY 10065, USALaboratory of Evolutionary Genetics and Genomics, The Rockefeller University, New York, NY 10065, USALaboratory of Evolutionary Genetics and Genomics, The Rockefeller University, New York, NY 10065, USALaboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, NY 10065, USA; Corresponding authorSummary: Cooperative binding of transcription factors (TFs) to chromatin orchestrates gene expression programming and cell fate specification. However, the biophysical principles of TF cooperativity remain incompletely understood. Here we use single-molecule fluorescence microscopy to study the partnership between Sox2 and Oct4, two core members of the pluripotency gene regulatory network. We find that the ability of Sox2 to target DNA inside nucleosomes is strongly affected by the translational and rotational positioning of its binding motif. In contrast, Oct4 can access nucleosomal sites with equal capacities. Furthermore, the Sox2-Oct4 pair displays nonreciprocal cooperativity, with Oct4 modulating interaction of Sox2 with the nucleosome but not vice versa. Such cooperativity is conditional upon the composite motif’s residing at specific nucleosomal locations. These results reveal that pioneer factors possess distinct chromatin-binding properties and suggest that the same set of TFs can differentially regulate gene activities on the basis of their motif positions in the nucleosomal context. : Using single-molecule fluorescence imaging, Li et al. investigate the pioneer activities of pluripotency factors Sox2 and Oct4 and find that they exhibit distinct nucleosome binding preferences as well as context-dependent cooperativity, which potentially allows gene-specific transcriptional regulation. Keywords: Sox2, Oct4, nucleosome, single-molecule fluorescence, pioneer activity, transcription factor, cooperative binding, gene regulatory networkhttp://www.sciencedirect.com/science/article/pii/S2211124719310198 |
| spellingShingle | Sai Li Eric Bo Zheng Li Zhao Shixin Liu Nonreciprocal and Conditional Cooperativity Directs the Pioneer Activity of Pluripotency Transcription Factors Cell Reports |
| title | Nonreciprocal and Conditional Cooperativity Directs the Pioneer Activity of Pluripotency Transcription Factors |
| title_full | Nonreciprocal and Conditional Cooperativity Directs the Pioneer Activity of Pluripotency Transcription Factors |
| title_fullStr | Nonreciprocal and Conditional Cooperativity Directs the Pioneer Activity of Pluripotency Transcription Factors |
| title_full_unstemmed | Nonreciprocal and Conditional Cooperativity Directs the Pioneer Activity of Pluripotency Transcription Factors |
| title_short | Nonreciprocal and Conditional Cooperativity Directs the Pioneer Activity of Pluripotency Transcription Factors |
| title_sort | nonreciprocal and conditional cooperativity directs the pioneer activity of pluripotency transcription factors |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719310198 |
| work_keys_str_mv | AT saili nonreciprocalandconditionalcooperativitydirectsthepioneeractivityofpluripotencytranscriptionfactors AT ericbozheng nonreciprocalandconditionalcooperativitydirectsthepioneeractivityofpluripotencytranscriptionfactors AT lizhao nonreciprocalandconditionalcooperativitydirectsthepioneeractivityofpluripotencytranscriptionfactors AT shixinliu nonreciprocalandconditionalcooperativitydirectsthepioneeractivityofpluripotencytranscriptionfactors |