TY - JOUR
T1 - SOX10 directly modulates ERBB3 transcription via an intronic neural crest enhancer
AU - Prasad, Megana K.
AU - Reed, Xylena
AU - Gorkin, David U.
AU - Cronin, Julia C.
AU - McAdow, Anthony R.
AU - Chain, Kristopher
AU - Hodonsky, Chani J.
AU - Jones, Erin A.
AU - Svaren, John
AU - Antonellis, Anthony
AU - Johnson, Stephen L.
AU - Loftus, Stacie K.
AU - Pavan, William J.
AU - McCallion, Andrew S.
N1 - Funding Information:
The authors would like to thank the Avramopoulos lab for their kind gift of Neuro2A cells and Seneca Bessling for her help with zebrafish husbandry. We would also like to thank Zachary Stine for critical scientific discussion and reading of the manuscript and also Grzegorz Burzynski for critical reading of the manuscript. Funding for this work comes from NIH/NIGMS and NIH/NINDS grants to ASM (GM071648 and NS062972), a NIGMS grant to SJ (GM056988), a NIH grant to JS (HD41590), a NIH/NINDS grant to AA (NS073748) and intramural NIH grants to WJP.
PY - 2011
Y1 - 2011
N2 - Background: The ERBB3 gene is essential for the proper development of the neural crest (NC) and its derivative populations such as Schwann cells. As with all cell fate decisions, transcriptional regulatory control plays a significant role in the progressive restriction and specification of NC derived lineages during development. However, little is known about the sequences mediating transcriptional regulation of ERBB3 or the factors that bind them. Results: In this study we identified three transcriptional enhancers at the ERBB3 locus and evaluated their regulatory potential in vitro in NC-derived cell types and in vivo in transgenic zebrafish. One enhancer, termed ERBB3-MCS6, which lies within the first intron of ERBB3, directs the highest reporter expression in vitro and also demonstrates epigenetic marks consistent with enhancer activity. We identify a consensus SOX10 binding site within ERBB3-MCS6 and demonstrate, in vitro, its necessity and sufficiency for the activity of this enhancer. Additionally, we demonstrate that transcription from the endogenous Erbb3 locus is dependent on Sox10. Further we demonstrate in vitro that Sox10 physically interacts with that ERBB3-MCS6. Consistent with its in vitro activity, we also show that ERBB3-MCS6 drives reporter expression in NC cells and a subset of its derivative lineages in vivo in zebrafish in a manner consistent with erbb3b expression. We also demonstrate, using morpholino analysis, that Sox10 is necessary for ERBB3-MCS6 expression in vivo in zebrafish. Conclusions: Taken collectively, our data suggest that ERBB3 may be directly regulated by SOX10, and that this control may in part be facilitated by ERBB3-MCS6.
AB - Background: The ERBB3 gene is essential for the proper development of the neural crest (NC) and its derivative populations such as Schwann cells. As with all cell fate decisions, transcriptional regulatory control plays a significant role in the progressive restriction and specification of NC derived lineages during development. However, little is known about the sequences mediating transcriptional regulation of ERBB3 or the factors that bind them. Results: In this study we identified three transcriptional enhancers at the ERBB3 locus and evaluated their regulatory potential in vitro in NC-derived cell types and in vivo in transgenic zebrafish. One enhancer, termed ERBB3-MCS6, which lies within the first intron of ERBB3, directs the highest reporter expression in vitro and also demonstrates epigenetic marks consistent with enhancer activity. We identify a consensus SOX10 binding site within ERBB3-MCS6 and demonstrate, in vitro, its necessity and sufficiency for the activity of this enhancer. Additionally, we demonstrate that transcription from the endogenous Erbb3 locus is dependent on Sox10. Further we demonstrate in vitro that Sox10 physically interacts with that ERBB3-MCS6. Consistent with its in vitro activity, we also show that ERBB3-MCS6 drives reporter expression in NC cells and a subset of its derivative lineages in vivo in zebrafish in a manner consistent with erbb3b expression. We also demonstrate, using morpholino analysis, that Sox10 is necessary for ERBB3-MCS6 expression in vivo in zebrafish. Conclusions: Taken collectively, our data suggest that ERBB3 may be directly regulated by SOX10, and that this control may in part be facilitated by ERBB3-MCS6.
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U2 - 10.1186/1471-213X-11-40
DO - 10.1186/1471-213X-11-40
M3 - Article
C2 - 21672228
AN - SCOPUS:79958279111
SN - 1471-213X
VL - 11
JO - BMC Developmental Biology
JF - BMC Developmental Biology
M1 - 40
ER -