Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Genome Biol. 2011;12(1):R2. doi: 10.1186/gb-2011-12-1-r2. Epub 2011 Jan 13.

Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis.

Author information

  • 1Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

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.

PMID:
21232103
[PubMed - indexed for MEDLINE]
PMCID:
PMC3091300
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for BioMed Central Icon for PubMed Central
    Loading ...
    Write to the Help Desk