|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online 2 December 2004
doi: 10.1242/dev.01548
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
* Author for correspondence (e-mail: kkroll{at}molecool.wustl.edu)
Accepted 28 October 2004
Chromatin remodeling complexes play crucial roles in transcription and are implicated in processes including cell proliferation, differentiation and embryonic patterning. Brg1 is the catalytic subunit of the SWI/SNF chromatin remodeling complex and shows neural-enriched expression. Although early lethality of Brg1-null mice reflects its importance in embryogenesis, this phenotype precluded further study of specific Brg1-dependent developmental processes. Here, we have identified a requirement of Brg1 for both Xenopus primary neurogenesis and neuronal differentiation of mammalian P19 embryonic carcinoma cells. In Xenopus, loss of Brg1 function did not affect neural induction or neural cell fate determination. However, the Sox2-positive, proliferating neural progenitor cell population was expanded, and expression of a terminally differentiated neuronal marker, N-tubulin, was diminished upon loss of Brg1 activity, suggesting that Brg1 is required for neuronal differentiation. The ability of the bHLH transcription factors Ngnr1 and NeuroD to drive neuronal differentiation was also abolished by loss of Brg1 function, indicating that Brg1 is essential for the proneural activities of Ngnr1 and NeuroD. Consistent with this, dominant-negative interference with Brg1 function in P19 cells suppressed neuronal differentiation promoted by NeuroD2, showing the requirement of Brg1 for neuronal differentiation is conserved in mammalian cells. Finally, we discovered that Brg1 physically associates with both Ngnr1 and NeuroD and that interference with Brg1 function blocks Neurogenin3- and NeuroD2-mediated reporter gene transactivation. Together, our results demonstrate that Brg1 (and by inference the SWI/SNF complex) is required for neuronal differentiation by mediating the transcriptional activities of proneural bHLH proteins.
Key words: Brg1, Chromatin remodeling, Differentiation, NeuroD, Neurogenesis, Neurogenin, P19, SWI/SNF, Xenopus
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Magnani and R. A Cabot Manipulation of SMARCA2 and SMARCA4 transcript levels in porcine embryos differentially alters development and expression of SMARCA1, SOX2, NANOG, and EIF1 Reproduction, January 1, 2009; 137(1): 23 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Heimeier, V. S. Hsia, and Y.-B. Shi Participation of Brahma-Related Gene 1 (BRG1)-Associated Factor 57 and BRG1-Containing Chromatin Remodeling Complexes in Thyroid Hormone-Dependent Gene Activation during Vertebrate Development Mol. Endocrinol., May 1, 2008; 22(5): 1065 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ochi, S. Hans, and M. Westerfield Smarcd3 Regulates the Timing of Zebrafish Myogenesis Onset J. Biol. Chem., February 8, 2008; 283(6): 3529 - 3536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Das, J. James, S. Bhattacharya, A. N. Imbalzano, M. L. Antony, G. Hegde, X. Zhao, K. Mallya, F. Ahmad, E. Knudsen, et al. SWI/SNF Chromatin Remodeling ATPase Brm Regulates the Differentiation of Early Retinal Stem Cells/Progenitors by Influencing Brn3b Expression and Notch Signaling J. Biol. Chem., November 30, 2007; 282(48): 35187 - 35201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mandel and I. Gozes Activity-dependent Neuroprotective Protein Constitutes a Novel Element in the SWI/SNF Chromatin Remodeling Complex J. Biol. Chem., November 23, 2007; 282(47): 34448 - 34456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Flora, J. J. Garcia, C. Thaller, and H. Y. Zoghbi The E-protein Tcf4 interacts with Math1 to regulate differentiation of a specific subset of neuronal progenitors PNAS, September 25, 2007; 104(39): 15382 - 15387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zhang, H. Fang, J. Zhou, and B. P. Herring A Novel Role of Brg1 in the Regulation of SRF/MRTFA-dependent Smooth Muscle-specific Gene Expression J. Biol. Chem., August 31, 2007; 282(35): 25708 - 25716. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Linder, E. Mentele, K. Mansperger, T. Straub, E. Kremmer, and R. A.W. Rupp CHD4/Mi-2beta activity is required for the positioning of the mesoderm/neuroectoderm boundary in Xenopus Genes & Dev., April 15, 2007; 21(8): 973 - 983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bilodeau, S. Vallette-Kasic, Y. Gauthier, D. Figarella-Branger, T. Brue, F. Berthelet, A. Lacroix, D. Batista, C. Stratakis, J. Hanson, et al. Role of Brg1 and HDAC2 in GR trans-repression of the pituitary POMC gene and misexpression in Cushing disease. Genes & Dev., October 15, 2006; 20(20): 2871 - 2886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. L. de la Serna, Y. Ohkawa, C. Higashi, C. Dutta, J. Osias, N. Kommajosyula, T. Tachibana, and A. N. Imbalzano The Microphthalmia-associated Transcription Factor Requires SWI/SNF Enzymes to Activate Melanocyte-specific Genes J. Biol. Chem., July 21, 2006; 281(29): 20233 - 20241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Heasman Patterning the early Xenopus embryo. Development, April 1, 2006; 133(7): 1205 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Olguin, P. Oteiza, E. Gamboa, J. L. Gomez-Skarmeta, and M. Kukuljan RE-1 silencer of transcription/neural restrictive silencer factor modulates ectodermal patterning during Xenopus development. J. Neurosci., March 8, 2006; 26(10): 2820 - 2829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Ge, F. He, K. J. Kim, B. Blanchi, V. Coskun, L. Nguyen, X. Wu, J. Zhao, J. I.-T. Heng, K. Martinowich, et al. Coupling of cell migration with neurogenesis by proneural bHLH factors PNAS, January 31, 2006; 103(5): 1319 - 1324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Seo, A. Herr, J.-W. Lim, G. A. Richardson, H. Richardson, and K. L. Kroll Geminin regulates neuronal differentiation by antagonizing Brg1 activity Genes & Dev., July 15, 2005; 19(14): 1723 - 1734. [Abstract] [Full Text] [PDF]
|
|
