Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis
Name
gb-2011-12-1-r2.pdf
Size
1.25 MB
Format
Adobe PDF
Checksum (MD5)
fb4a8f0d2af14a7f9dff9e9fd1c4f2a5
Author(s)
Mahony, Shaun
McCuine, Scott
Wichterle, Hynek
Gifford, David K.
Mazzoni, Esteban O.
Young, Richard A.
Date Issued
January 2011
Journal
Genome Biology
Publisher
BioMed Central Ltd
Citation
Genome Biology. 2011 Jan 13;12(1):R2
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1186/gb-2011-12-1-r2
