Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis
Abstract Background Among its many roles in development, retinoic acid determines the anterior-posterior identity of differentiating motor neurons by activating retinoic acid receptor (RAR)-mediated transcription. RAR is thought to bind the genome constitutively, and only induce transcription in...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
BioMed Central Ltd.
2011
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| Online Access: | http://hdl.handle.net/1721.1/65633 https://orcid.org/0000-0003-1709-4034 |
| _version_ | 1826213815179542528 |
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| author | Mahony, Shaun Mazzoni, Esteban O. McCuine, Scott Young, Richard A. Wichterle, Hynek Gifford, David K. |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Mahony, Shaun Mazzoni, Esteban O. McCuine, Scott Young, Richard A. Wichterle, Hynek Gifford, David K. |
| author_sort | Mahony, Shaun |
| collection | MIT |
| description | Abstract
Background
Among its many roles in development, retinoic acid determines the anterior-posterior identity of differentiating motor neurons by activating retinoic acid receptor (RAR)-mediated transcription. RAR is thought to bind the genome constitutively, and only induce transcription in the presence of the retinoid ligand. However, little is known about where RAR binds to the genome or how it selects target sites.
Results
We tested the constitutive RAR binding model using the retinoic acid-driven differentiation of mouse embryonic stem cells into differentiated motor neurons. We find that retinoic acid treatment results in widespread changes in RAR genomic binding, including novel binding to genes directly responsible for anterior-posterior specification, as well as the subsequent recruitment of the basal polymerase machinery. Finally, we discovered that the binding of transcription factors at the embryonic stem cell stage can accurately predict where in the genome RAR binds after initial differentiation.
Conclusions
We have characterized a ligand-dependent shift in RAR genomic occupancy at the initiation of neurogenesis. Our data also suggest that enhancers active in pluripotent embryonic stem cells may be preselecting regions that will be activated by RAR during neuronal differentiation. |
| first_indexed | 2024-09-23T15:55:16Z |
| format | Article |
| id | mit-1721.1/65633 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:55:16Z |
| publishDate | 2011 |
| publisher | BioMed Central Ltd. |
| record_format | dspace |
| spelling | mit-1721.1/656332022-09-29T17:03:16Z Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis Mahony, Shaun Mazzoni, Esteban O. McCuine, Scott Young, Richard A. Wichterle, Hynek Gifford, David K. Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Gifford, David K. Mahony, Shaun Gifford, David K. Abstract Background Among its many roles in development, retinoic acid determines the anterior-posterior identity of differentiating motor neurons by activating retinoic acid receptor (RAR)-mediated transcription. RAR is thought to bind the genome constitutively, and only induce transcription in the presence of the retinoid ligand. However, little is known about where RAR binds to the genome or how it selects target sites. Results We tested the constitutive RAR binding model using the retinoic acid-driven differentiation of mouse embryonic stem cells into differentiated motor neurons. We find that retinoic acid treatment results in widespread changes in RAR genomic binding, including novel binding to genes directly responsible for anterior-posterior specification, as well as the subsequent recruitment of the basal polymerase machinery. Finally, we discovered that the binding of transcription factors at the embryonic stem cell stage can accurately predict where in the genome RAR binds after initial differentiation. Conclusions We have characterized a ligand-dependent shift in RAR genomic occupancy at the initiation of neurogenesis. Our data also suggest that enhancers active in pluripotent embryonic stem cells may be preselecting regions that will be activated by RAR during neuronal differentiation. Damon Runyon Cancer Research Foundation (DRG-1937-07) National Institutes of Health (U.S.) (P01 NS055923) 2011-09-09T18:49:34Z 2011-09-09T18:49:34Z 2011-01 2010-12 Article http://purl.org/eprint/type/JournalArticle 1474-7596 1474-760X http://hdl.handle.net/1721.1/65633 Mahony, Shaun et al. “Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis.” Genome Biology 12 (2011): R2. https://orcid.org/0000-0003-1709-4034 en_US http://dx.doi.org/10.1186/gb-2011-12-1-r2 Genome Biology Creative Commons Attribution http://creativecommons.org/licenses/by/2.0/ application/pdf BioMed Central Ltd. BMC |
| spellingShingle | Mahony, Shaun Mazzoni, Esteban O. McCuine, Scott Young, Richard A. Wichterle, Hynek Gifford, David K. Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis |
| title | Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis |
| title_full | Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis |
| title_fullStr | Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis |
| title_full_unstemmed | Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis |
| title_short | Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis |
| title_sort | ligand dependent dynamics of retinoic acid receptor binding during early neurogenesis |
| url | http://hdl.handle.net/1721.1/65633 https://orcid.org/0000-0003-1709-4034 |
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