Education

• B.A. in Biology, Augustana College, 1985
• Ph.D. in Molecular Physiology and Biophysics, Vanderbilt University, 1992

Research

• Role of EGR and NAB proteins in peripheral nerve myelination.
  
• Mechanism and Regulation of NAB Corepressor Function.
  
• Role of Chromatin Structure in Gene Regulation.
  

My lab studies regulation of gene expression by the EGR (early growth response) transcriptional activators. Several groups have identified human EGR2 mutations that cause myelination disorders of the peripheral nervous system such as Congenital Hypomyelinating Neuropathy (CHN), Charcot-Marie-Tooth Disease (CMT), and Dejerine-Sottas Syndrome (DSS). Association of EGR2 mutations with such myelination disorders is consistent with the phenotype of EGR2/Krox20 knockout mice which also exhibit a profound myelination defect. However, an unexpected result was that most of the EGR2 mutants in the human diseases appear to exert a dominant negative effect, and we are currently characterizing the molecular interactions that are responsible for this phenomenon. EGR2 has been identified as a master regulator of a diverse array of myelin-associated genes, and we have recently been able to use chromatin immunoprecipitation (ChIP) to localize EGR2 binding sites in myelinating peripheral nerve in vivo, and we are using this technique to explore interactions with other transcription factors and histone modifications in myelin genes.

One of the EGR2 mutations associated with a profound peripheral neuropathy has demonstrated that interaction of EGR2 with NAB corepressors is critical for proper control of peripheral nerve myelination.� NAB1 and NAB2 are highly related proteins that modulate transcription of EGR target genes via direct binding to three members of the EGR family: EGR1/NGFI-A, EGR2/Krox20, and EGR3. At the molecular level, we are interested in probing the mechanism of how interactions between EGR and NAB proteins regulate transcription of EGR target genes. Recently, we have shown that NAB proteins interact with the CHD4 subunit of the NuRD (Nucleosome Remodeling and Deacetylase) complex, indicating that NAB proteins manipulate chromatin structure of target genes.

Responsibilities

Associate Professor

• Course Coordinator for Molecular and Metabolic Basis of Medicine

Graduate Training

• Program in Cellular and Molecular Biology
   
• Molecular Biosciences Training Grant
   
• Molecular and Cellular Pharmacology Program
   
• Comparative Biomedical Sciences Graduate Program

Affiliations

• Waisman Center
   
• University of Wisconsin Comprehensive Cancer Center

Recent Publications

Jang, S.W., LeBlanc, S.E., Roopra, A., Wrabetz, L., and Svaren, J. (2006) In vivo detection of Egr2 binding to target genes during peripheral nerve myelination, Journal of Neurochemistry, 98:1678-1687 [Abstract]

Srinivasan, R., Mager, G.M., Ward, R.M., Mayer, J., and Svaren, J. The NAB2 corepressor interacts with the CHD4 subunit of the NuRD complex (2006) Journal of Biological Chemistry, 281:15129-15137 [Abstract]

LeBlanc, S.E., Jang, S.W., Ward, R.M., Wrabetz, L., and Svaren, J. Direct Regulation of Myelin Protein Zero Expression by the Egr2 Transactivator (2006) Journal of Biological Chemistry, 281:5453-5460. [Abstract]

LeBlanc, S.E., Srinivasan, R., Mager, G.M., Gillian-Daniel, A.L., Wrabetz, L. and Svaren, J. (2005) Regulation of lipid/cholesterol biosynthetic genes by Egr2/Krox-20 during peripheral nerve myelination. Journal of Neurochemistry, 93:737-748. [Abstract]

Gillian-Daniel, A.L. and Svaren, J.(2004) The Ddx20/DP103 Dead Box Protein represses transcriptional activation by Egr2/Krox-20. Journal of Biological Chemistry, 279:9056-63 [Abstract]

Venken, K., Di Maria, E., Bellone, E.,Balestra, P., Cassandrini, D., Mandich, P., DeJonghe, P., Timmerman, V., Svaren, J. (2002) Search for mutations in the EGR2 corepressor proteins, NAB1 and NAB2, in human peripheral neuropathies. Neurogenetics, 4:37-41. [Abstract]

Nagarajan, R., Svaren, J., Le, N., Araki T., Watson, M., and Milbrandt, J. (2001) EGR2 mutations in inherited neuropathies dominant negatively inhibit myelin gene expression. Neuron, 30:355-368 Full text

Svaren, J., Ehrig, T., Abdulkadir, S.A., Ehrengruber, M.U., Watson, M.A., and Milbrandt, J.(2000) EGR1 Target Genes in Prostate Carcinoma Cells identified by Microarray Analysis. Journal of Biological Chemistry 275,38524-38531. Full text

Sevetson, B., Svaren, J., and Milbrandt, J. (2000) A Novel Activation Function for NAB Proteins in EGR-dependent Transcription of the Luteinizing Hormone (LH ) Gene. Journal of Biological Chemistry 275, 9749-9757. Abstract Full Text

Warner, L.E., Svaren, J., Milbrandt, J., and Lupski, J.R. (1999) Functional consequences of mutations in the early growth response 2 (EGR2) gene associated with human myelinopathies. Human and Molecular Genetics 8, 1245-1251. Abstract

Svaren, J., Sevetson, B.R., Golda, T., Stanton, J., Swirnoff, A.H., and Milbrandt, J. (1998) Novel Mutants of NAB Corepressors Enhance Activation by Egr Transactivators. EMBO Journal 17, 6010-6019. Abstract Full Text

Svaren, J. and Hörz, W. (1997) Transcription factors vs. Nucleosomes: regulation of the PHO5 promoter in yeast. Trends in Biochemical Sciences 22, 93-97. Abstract

Svaren, J., Apel, E.D., Simburger, K.S., Jenkins, N.A., Gilbert, D.J., Copeland, N.A., and Milbrandt, J. (1997) The Nab2 and Stat6 Genes Share a Common Transcription Termination Region. Genomics 41, 33-39. Abstract

Svaren, J., Sevetson, B.R., Apel, E.D., Zimonjic, D.B., Popescu, N.C., and Milbrandt, J. (1996) NAB2, a Corepressor of NGFI-A (Egr-1) and Krox20, is Induced by Proliferative and Differentiative Stimuli. Molecular and Cellular Biology 16, 3545-3553. Abstract Full Text

Svaren, J. and Hörz, W. (1996) Regulation of Gene Expression by Nucleosomes. Current Opinion in Genetics and Development 6, 164-170. Abstract