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The Journal of Neuroscience, February 1, 2000, 20(3):1073-1084

Septamer Element-Binding Proteins in Neuronal and Glial Differentiation

Albert Dobi^{1, 2}, Miklos Palkovits³, Christina G. Palkovits¹, Mary A. Ring^{1, 2}, and Denes v. Agoston^{1, 2}

¹ Laboratory of Developmental Neurobiology, National Institute of Child Health and Development, National Institutes of Health, Bethesda, Maryland 20892, ² Department of Anatomy and Cell Biology and Program in Neuroscience, School of Medicine, Uniformed Services University, Bethesda, Maryland 20814, and ³ Laboratory of Genetics, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892

Differentiation of progenitors into neurons and glia is regulated by interactions between regulatory DNA elements of neuron- and glia-specific genes and transcription factors that are differentially expressed by progenitors at progressive stages of neural development. We have identified a novel DNA regulatory element (TTTGCAT = septamer) present on the enkephalin (ENK), neuronal cell adhesion molecule, neurofilament of 68 kDa (NF68), growth-associated protein of 43 kDa, glial high-affinity glutamine transporter, tyrosine hydroxylase, etc., genes. When septamer function was blocked by introducing septamer competitor DNA into primary differentiating neural cultures, mRNA levels of ENK, NF68, and glial fibrillary acidic protein decreased by 50-80%, whereas no effect was seen using a control DNA. Septamer elements serve as binding sites for lineage-specific multimeric complexes assembled from three distinct nuclear proteins. Progenitors express a 16 kDa protein (p-sept) which binds to DNA as a homodimer (detected as the 32 kDa P-band). Cells that entered the neuronal lineage express an additional 29 kDa protein (n-sept) that binds to the homodimerized p-sept, and together they form a 62 kDa multimer (detected as N-band). Cells that entered the glial lineage express a distinct 23 kDa protein (g-sept), which along with the homodimerized p-sept form a 56 kDa multimer (observed as G-band). The binding of the distinct protein complexes (P, G, and N) to the septamer site causes a lineage-specific DNA bending (P = 53°; G = 72°; and N = 90°), which may contribute to the regulatory effect of the septamer interaction. In summary, septamer and its binding proteins represent novel protein-DNA interactions that may contribute to the regulation of neuroglial differentiation in the developing mammalian CNS.

Key words: progenitors; neuron; glia; development; DNA molecular decoy; DNA bending

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Copyright © 2000 Society for Neuroscience  0270-6474/00/2031073-12$05.00/0

This article has been cited by other articles:

				A. Dobi, M. Szemes, C. Lee, M. Palkovits, F. Lim, A. Gyorgy, M. A. Mahan, and D. V. Agoston AUF1 Is Expressed in the Developing Brain, Binds to AT-rich Double-stranded DNA, and Regulates Enkephalin Gene Expression J. Biol. Chem., September 29, 2006; 281(39): 28889 - 28900. [Abstract] [Full Text] [PDF]

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