Graduated in 1978 at the University of North Carolina, Chapel Hill. (Mentor: Dr. Darrel Stafford)
Postdoctoral Studies (1979-1982) with Dr. Bill Marzluff, Florida State University
Assistant Professor (1982-1988), Department of Biochemistry, UMMC
Associate Professor (1988-1997), Department of Biochemistry, UMMC
Professor (1997-Present), Department of Biochemistry, UMMC
Genomics Facility
Don Sittman, Ph.D., Facility Director
Basis of the Functional Differences Among H1 Histone Variants.
Eukaryotic DNA is packaged in the form of chromatin. The structure of chromatin is important in the regulation of gene expression and replication of DNA. The H1 or linker histones are a family of chromosomal proteins that are responsible for condensing chromatin into higher order conformation, and accordingly play a major role in the regulation of transcription and replication. The mechanisms, by which H1s facilitate higher order packaging of chromatin, as well as the role of each of the different H1 variants in the packaging process, are unknown. The long-term goal of my lab's research is to better define the role of H1s in chromatin by identifying the structural features responsible for functional differences among H1 variants. Our in vivo approach is to overproduce individual H1 variants and mutant H1s, that we have constructed, in tissue culture cells to study their effect on cell cycle progression, gene expression and chromatin structure. Presently, using this overexpression system, we are doing DNA microarray analysis and other techniques to assess the global differences in gene expression caused by particular H1 variants.
Histone Related Publications
Sittman, D.B., Chiu, I-M., Pan, C-J., Cohn, R.H., Kedes, L.H. and Marzluff, W.F. Isolation of two clusters of mouse histone genes. Proc. Natl. Acad. Sci. USA 78: 4078-4082, 1981.
Sittman, D.B., Graves, R.A. and Marzluff, W.F. Histone mRNA Concentrations are regulated at the level of transcription and mRNA degradation. Proc. Natl. Acad. Sci. USA 80: 1849-1853, 1983.
Sittman, D.B., Graves, R.A. and Marzluff, W.F. Structure of a cluster of mouse histone genes. Nucl. Acids Res.
11: 6679-6697, 1983.
Brown, D.T., Wellman, S.E. and Sittman, D.B. Changes in the levels of three different classes of histone mRNA during murine erythroleukemia cell differentiation. Mol. & Cell Biol. 5: 2879-2886, 1985.
Wellman, S.E., Casano, P.J., Pilch, D.R., Marzluff, W.F. and Sittman, D.B. Characterization of mouse H3.3-like histone genes. Gene 59: 29-39,1987.
Yang, Y-S., Brown, D.T., Wellman, S.E. and Sittman, D.B. Isolation and characterization of a mouse fully replication-dependent H1 gene within a genomic cluster of core histone genes. J. Biol. Chem. 262: 17118-17125, 1987.
Brown, D.T., Yang, Y-S. and Sittman, D.B. Histone gene switching in murine erythroleukemia cells is differentiation specific and occurs without loss of cell cycle regulation. Mol. & Cell. Biol. 8: 4406-4415, 1988.
Brown, D.T. and Sittman, D.B. Identification through overexpression and tagging of the variant type of mouse H1e and H1c genes. J. Biol. Chem. 268: 713-718, 1993.
Wellman, S.E., Sittman, D.B., and Chaires, J.B. Preferential binding of the H1e Histone to GC-rich DNA. Biochemistry 33: 384-388, 1994.
Dong, Y., Sirotkin, A.M., Yang, Y., Brown, D.T., Sittman, D.B., and Skoultchi, A.I. Isolation and characterization of the replication-dependent mouse H1 histone genes. Nucleic Acids Res. 22: 1421-1428, 1994.
Brown, D.T., Alexander, B.T., and Sittman, D.B. Differential effect of H1 variant overexpression on cell cycle progression and gene expression. Nucleic Acids Res. 24: 486-493, 1996.
Brown, D.T., Gunjan, A., Alexander, B.T. and Sittman, D.B. Differential effect of H1 variant overproduction on gene expression is due to differences in the central globular domain. Nucl. Acids Res. 25: 5003-5009, 1997.
Lu, Z.H., Sittman, D.B., Brown, D.T., Munshi, R. and Leno, G.H. Histone H1 modulates DNA replication through multiple pathways Xenopus egg extract. J. Cell Sci. 110: 2745-2758, 1997.
Lu, Z.H., Sittman, D.B., Romanowski, P., and Leno, G.H. Histone H1 reduces the frequency of initaition of Xenopus Egg extract by limiting the assembly of pre-replication complexes on sperm chromatin. Mol. Biol. Cell. 9: 1163-1176, 1998.
Gunjan, A., Alexander, B.T., Sittman, D.B., and Brown, D.T. Effects of H1 histone variant overexpression on chromatin structure. J. Biol. Chem. 274: 37950-37956, 1999.
Gunjan, A., Sittman, D.B., and Brown, D.T. Core histone acetylation is regulated by linker histone stoichiometry in vivo . J. Biol. Chem. 276: 3635-3640, 2001.
De, S., Brown, D.T., Lu, Z.H., Leno, G.H., Wellman, S.E., and Sittman, D.B. Histone H1 variants differentially inhibit DNA replication through an affinity for chromatin mediated by their carboxyl-terminal domains. Gene 292: 173-181, 2002.
Alam, N. and Sittman, D. B. Characterization of theCytotoxic Effect of a Chimeric Restriction Enzyme, H1°- FokI. Gene Therapy and Molecular Biology 10: 147-160,2006
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