Blaine Bartholomew received his B.S. degree in chemistry from Brigham Young University in August 1982 and his Ph.D. degree from the University of California, Davis in March 1988. He was awarded a postdoctoral fellowship from the American Cancer Society from 1988 to 1991 to study at the University of California, San Diego and joined SIUC in August 1991.
phone: (618) 453-6437
email: bbartholomew@siumed.edu
I study two different aspects of regulation of eukaryotic gene expression. First, gene expression is controlled to a large extent be regulating the four different stages of transcription; namely, (1) promoter binding and activation, (2) RNA chain initiation and promoter escape, (3) elongation and (4) termination and release of RNA transcripts. I focus on studying the molecular interactions involved in the assembly and activation of the transcription complex and how the transcription complex changes during the process of initiation and elongation of RNA. I have helped pioneer the approach of studying these large protein-DNA complexes by mapping the interactions of protein with DNA and RNA with base-pair resolution by DNA photoaffinity (D*P) and RNA photoaffinity (R*P) labeling. Each DNA and RNA probe has photoreactive residue(s) incorporated at specific sites within that molecule for covalently tagging the protein surface in contact with that region of DNA or RNA. It is possible to determine which region of the protein interacts with specific positions in DNA or RNA by peptide mapping the D*P and R*P labeled proteins . The dynamic nature of the transcription complex is also examined by doing rapid photoaffinity labeling. Second, I also study the process of chromatin remodeling that is crucial for helping to reorganize the chromatin bound DNA so that the transcriptional machinery can bind. Making the DNA accessible for transcription is as key a process as is the regulation of the transcription process itself for gene expression. Large protein complexes remodel chromatin that hydrolyze ATP in the process. I study the yeast chromatin remodeling complex called SWI/SNF that is 2 megadaltons in size and has 11 different subunits. My research has been to determined how SWI/SNF changes the histone-DNA contacts in chromatin and how does SWI/SNF interact with the nucleosome core particle. Work is also ongoing in the development of protein-protein crosslinking techniques to elucidate important details of protein-protein interactions involved in chromatin remodeling and transcription.
This research is funded by the National Institute of Health.
Chromatin
Transcription
For more information about this work or those in the lab please go to the Bartholomew Lab Home Page
1. Sengupta, S.M., Persinger, J., Bartholomew, B. and Peterson, C.L. (1999) Methods 19, 434-446 . Use of DNA photoaffinity labeling to study nucleosome remodeling by SWI/SNF. ABSTRACT-MEDLINE
2. Persinger, J. and Bartholomew, B. (in press) edited by T. Moss in "Methods in Molecular Biology: Protein-DNA Interaction Protocols". Site-specific DNA photoaffinity labeling of RNA polymerase III transcription complexes.
3. Persinger, J., Sengupta, S.M., and Bartholomew, B. (1999) Mol. Cell. Biol. 19, 5218-5234, Spatial Organization of the Core Region of Yeast TFIIIB-DNA Complexes. ABSTRACT-MEDLINE
4. Michelson, R.J., Collard, M.W., Ziemba, A.J., Persinger, J., Bartholomew, B., and Huggenvik, J.I. (1999) J. Biol. Chem. 274, 30510-30519. Nuclear DEAF-1 related (NUDR) Protein Contains a Novel DNA Binding Domain and Represses Transcription of the Heterogeneous Nuclear Ribonucleoprotein A2/B1 Promoter. ABSTRACT-MEDLINE
5. Tate, J.J., Persinger, J., and Bartholomew, B. (1998) Nucleic Acids Res., 26, 1421-1426. Survey of four different photoreactive moieties for DNA photoaffinity labeling of yeast RNA polymerase III transcription complexes. ABSTRACT-MEDLINE
6. Radebaugh, C.A., Gong, X., Bartholomew, B. and Paule, M.R. (1997) J. Biol. Chem., 272, 3141-3144. Identification of Previously Unrecognized Common Elements in Eukaryotic Promoters: a Ribosomal RNA Initiator Element for RNA Polymerase I. ABSTRACT MEDLINE
7. Persinger, J. and Bartholomew, B. (1996) J. Biol. Chem., 271, 33039-33046. Mapping the Contacts of Yeast TFIIIB and RNA Polymerase III at Various Distances from the Major Groove of DNA by DNA Photoaffinity Labeling. ABSTRACT-MEDLINE
8. Pruss, D., Bartholomew, B., Persinger, J., Hayes, J., Arents, G., Moudrianakis, E.N., and Wolffe, A.P. (1996) Science 274, 614-617. A new model for the nucleosome: a binding site for linker histones inside the DNA gyres. ABSTRACT-MEDLINE
9. Powell, W., Bartholomew, B., and Rienes, D. (1996) J.Biol.Chem. 271, 22301-22304. Elongation Factor SII Contacts the 3' End of RNA in RNA Polymerase II Elongation Complex. ABSTRACT-MEDLINE
10. Lannutti, B.J., Persinger, J. and Bartholomew, B. (1996) Biochemistry 35, 9821-9831. Probing the protein-DNA Contacts of a Yeast RNA Polymerase III Transcription Complex in a Crude Extract: Solid Phase Synthesis of DNA Photoaffinity Probes Containing a Novel Photoreactive Deoxycytidine Analog. ABSTRACT-MEDLINE
11. Bartholomew, B., Tinker, R.L., Kassavetis, G.A., and Geiduschek, E.P. (1995) Methods Enzymol. 262, 729-753. Photochemical Cross-linking Assay for DNA Tracking by Replication Proteins. ABSTRACT-MEDLINE
12. Bartholomew, B., Braun, B.R., Kassavetis, G.A., and Geiduschek, E.P. (1994) J.Biol.Chem. 269, 18090-18095. Probing Close DNA Contacts of RNA Polymerase III Transcription Complexes with the Photoactive Nucleoside 4-Thiodeoxythymidine. ABSTRACT-MEDLINE
13. Kassavetis, G.A., Bardeleben, C., Bartholomew, B., Braun, B.R., Joazeiro, C.A., Pisano, M. and Geiduschek, E.P. (1994) edited by J.W. Conaway and R.C. Conaway, in "Transcription Mechanisms and Regulation" Raven Press, New York. Transcription by RNA polymerase III.
14. Bartholomew, B., Durkovich, D., Kassavetis, G.A., and Geiduschek. E.P. (1993) Mol.Cell.Biol. 13, 942-952. Orientation and Topography of RNA Polymerase III in Transcription Complexes. ABSTRACT-MEDLINE
15. Braun, B.R., Bartholomew, B., Kassavetis, G.A., and Geiduschek, E.P. (1993) J. Mol.Biol. 228, 1063-1077. Topography of Transcription Factor Complexes on the Saccharomyces cerevisiae 5S RNA Gene. ABSTRACT-MEDLINE
16. Bartholomew, B., Kassavetis, G.A., and Geiduschek, E.P. (1991) Mol.Cell.Biol. 11, 5181-5189. Two Components of S. cerevisiae TFIIIB are Stereospecifically Located Upstream of a tRNA Gene and Interact with the Second Largest Subunit of TFIIIC. ABSTRACT-MEDLINE
17. Kassavetis, G.A., Bartholomew, B., Blanco, J.A., Johnson, T.E., and Geiduschek, E.P. (1991) Proc.Natl.Acad.Sci.USA 88, 7308-7312. Two Essential Components of the Saccharomyces cerevisiae Transcription Factor IIIB:Transcription and DNA-binding Properities. ABSTRACT-MEDLINE
18. Bartholomew, B., Kassavetis, G.A., Braun, B.R., and Geiduschek, E.P. (1990) EMBO J. 9, 2197-2205. The Subunit Structure of Saccharomyces cerevisiae Transcription Factor IIIC Probed with a Novel Photocrosslinking Reagent. ABSTRACT-MEDLINE
19. Bartholomew, B., Meares, C.F., and Dahmus, M.E. (1990) J.Biol.Chem. 265, 3731-3737. Photoaffinity Labeling of RNA Polymerase III Transcription Complexes by Nascent RNA. ABSTRACT-MEDLINE
20. Dahmus, M.E., Bartholomew, B., Cadena, D.L., Dahmus, G.K., Kim, W-Y., Laybourn, P.J., and Payne, J. (1990) "Activation of Hormone and Growth Factor Receptors", 105-117. The Regulation of RNA polymerase II Activity by Multisite Phosphorylation.
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