Research Interests:

My major research interests are in the area of H1 histone-DNA interactions. The H1 histones are involved in packaging of eukaryotic chromatin, but the details of the interactions between H1 histones and DNA are not known. In mammalian cells, there is a family of H1 histone variants; the variants have distinct patterns of expression and are correlated with different levels of chromatin activity. Recent data suggest that there are functional differences among the variants in their interactions with DNA; for example, do they bind preferentially to particular DNA sequences, and is the selectivity different for different variants? We have investigated the mode of binding of the protein to the DNA and demonstrated that binding occurs in the major groove as well as in the minor groove. Understanding H1-DNA interactions may help us to understand why some DNA-binding drugs are efficacious in treatment of diseases and other DNA-binding drugs are not. For example, for many DNA-binding drugs, the affinity, sequence preference, and mode of binding are known; perhaps the efficacious drugs bind preferentially to sites (sequences or structural features) that are not preferred by the H1 histones, whereas the ineffective drugs bind to the same sites as, but are unable to effectively compete with, the H1 histones.

Selected Publications:

Wellman, S.E., Y. Song, D. Su, and N. Mamoon. (1997) Purification of mouse H1 histones expressed in E. coli. Biotechnology and Applied Biochem. 26: 117-123.

Wellman, S. E., Y. Song, and N. Mamoon. (1999) Sequence Preference of mouse H1(0) and H1t. Biochemistry 38: 13112-13118.

Spink, C. and S.E. Wellman. (2001) Thermal denaturation as a tool to study DNA ligand interactions. Meth. Enzymol. 340, 193-211. 

Kramer, R.E., S.E. Wellman, R.W. Rockhold, and R.C. Baker. (2002) Pharmacokinetics of methyl parathion: a comparison following single intravenous, oral or dermal administration. J. Biomed. Sci. 9: 311-320.  

Mamoon, N, Y. Song, and S.E. Wellman. (2002) Histone H1(0) and its carboxyl-terminal domain bind in the major groove of DNA. Biochemistry 41: 9222-9228.

De, S., Z. Brown, G. Lu, S. Leno, S. Wellman, and D. Sittman (2002) Histone H1 variants differentially inhibit DNA replication through an affinity for chromatin mediated by their carboxyl terminal domains. Gene 292: 173-181. 

Mamoon, N., Y. Song, S.E. Wellman. (2005)  Binding of histone H1 to DNA is described by an allosteric model.  Biopolmers 77: 9-17. 

Links of Interest:

The RCSB Protein Databank
http://www.rcsb.org/pdb/