Blaine Bartholomew received his B.S. degree in chemistry from Brigham Young University in 1982 and his Ph.D. degree from the University of California, Davis in 1988. He was a Postdoctoral Fellow of the American Cancer Society at the University of California, San Diego and joined SIUC in 1991. He received the Outstanding Scholar Award (School of Medicine) in 2006.
phone: (618) 453-6437
email: bbartholomew@siumed.edu
The importance of nucleosome structure and composition, as well as genomic positioning of nucleosomes, in processes that involve DNA has been extensively shown over the last decade. The accumulation of this type of data only appears to be accelerating as more attention is drawn to the epigenome and the factors that regulate its function. One group of complexes that have a crucial role in regulating chromatin structure and function is the class of ATP-dependent chromatin remodelers. At the simplest level these remodelers mobilize nucleosomes and can reposition them from thermodynamically preferred to non-preferred sites. The purpose of such rearrangements may be merely to occlude certain regulatory sites within the genome in order to make those sites inaccessible to their regulatory factors. Otherwise, the positioning of nucleosomes might be vital for establishment of particular higher-order chromatin structures that cause the DNA to become even less accessible than nucleosome binding alone. Although nucleosome mobilization or what is frequently referred to as “sliding” is a basic property of these remodelers, repositioning of nucleosomes is not their only function. ATP-dependent chromatin remodelers are also involved in the active exchange of histone variants into specialized chromatin regions such as centromeres and other genomic locations. Regions of chromosomes with particular functions such as centromeres or heterochromatin boundaries are demarcated by the preferential incorporation of histone variants such as CENPA and H2A.Z, and require these remodelers for their proper formation. A third property of these remodelers is not just to exchange part of the histones within the nucleosome, but to entirely disassemble nucleosomes and create nucleosome-free stretches on DNA.
In Saccharomyces cerevisiae there is a minimum of nine or more different ATP-dependent chromatin remodelers and in humans the lowest estimate is well over 30 different complexes. While significant progress has been made in identifying the roles of various remodelers in transcription activation/repression, DNA repair and replication, stem cell self renewal, and cell development; there is less understanding as to how the enzymatic activities of these complexes differ from one another. Some of the complexity could be due to alternative ways of recruiting complexes to distinct genomic sites, but it seems unlikely that recruitment is the main reason leading to the diversity of remodelers. Remodelers differ from each other in their underlying core subunits including the catalytic subunit and the remodeler specific accessory subunits thus creating a broad repertoire of remodelers. There are many important functional differences other than recruitment in the family of ATP-dependent chromatin remodelers which will be uncovered by acquiring a more comprehensive understanding of their biochemical properties.
1. Udugama, M., Sabri, A, and B. Bartholomew (2011) Mol Cell Biol 31, 662-673. The INO80 ATP-dependent chromatin remodeling complex is a nucleosome spacing factor.
2. Dechassa ML, Sabri A, Pondugula S, Kassabov SR, Chatterjee N, Kladde MP and B. Bartholomew (2010) Mol Cell 38(4), 590-602. SWI/SNF has intrinsic nucleosome disassembly activity that is dependent on adjacent nucleosomes.
3. Gangaraju VK, Prasad P, Srour A, Kagalwala MN, and B. Bartholomew (2009) Mol Cell, 35(1), 58-69. Conformational changes associated with template commitment in ATP-dependent chromatin remodeling by ISW2.
4. Dechassa ML, Zhang B, Horowitz-Scherer R, Persinger J, Woodcock CL, Peterson CL, Bartholomew B. (2008) Mol Cell Biol., 28(19), 6010-21. Architecture of the SWI/SNF-nucleosome complex.
5. Dang W. and B. Bartholomew, (2007) Mol Cell Biol,. 27(23), 8306-17. Domain architecture of the catalytic subunit in the ISW2-nucleosome complex.
6. Dang. W. Kagalwala MN, Bartholomew B. (2007) J. Biol. Chem 2007. 282(27), 19418-25. The Dpb4 subunit of ISW2 is anchored to extranucleosomal DNA.
7. Gangaraju, VK and Bartholomew, B (2007) Mol. Cell. Biol. 27, 3217-25. Molecular basis of nucleosome spacing: Two different modes of ISW1a binding to nucleosomes.
8. Zofall, M, Persinger, J., Kassabov, S.R. and Bartholomew (2006) Nat.Struct.Mol.Biol. 13, 339-346. Chromatin remodeling by ISW2 and SWI/SNF require DNA translocation inside the nucleosome.
9. Dang,W, Kagalwala, MN, and Bartholomew, B (2006) Mol. Cell. Biol. 26, 7388-96. Regulation of ISW2 by concerted action of histone H4 tail and extranucleosomal DNA.
10. Zofall, M, Persinger, J and Bartholomew, B. (2004) Mol. Cell. Biol. 24, 11047-10057. Functional role of extranucleosomal DNA and the entry site of the nucleosome in chromatin remodeling by ISW2.
11. Kagalwala MN, Glaus BJ, Dang, W., Zofall M, and Bartholomew B. (2004) EMBO J . 23 (10), 2092-2104. Topography of the ISW2-Nucleosome Complex: Insights into the Mechanism of ATP-dependent Chromatin Remodeling by ISW2.
12. Kassabov, S.K., Zhang, B., Persinger, J., and Bartholomew, B. (2003) Mol. Cell 11, 391-403. SWI/SNF Unwraps, Slides and Rewraps the Nucleosome.
1. Sen, P. Chatterjee, N., and Bartholomew, B. (2010) “SWI/SNF Chromatin Remodeling Complex” in Encyclopedia of Signaling Molecules, Springer Publishers.
2. Hota, S.K. and Bartholomew B. (2010) “Approaches for Studying Nucleosome Movement by ATP-dependent Chromatin Remodeling Complexes”, chapter in Methods in Molecular Biology, Springer Publishers.
3. Hota, S.K., Dechassa M.L., Prasad, P. and Bartholomew, B. (2010) “Mapping protein-DNA and protein-protein interactions of ATP-dependent chromatin remodelers”, chapter in Methods in Molecular Biology, Springer Publishers.
4. Persinger, J. and Bartholomew, B. (2009) edited by T. Moss in "Methods in Molecular Biology: Protein-DNA Interaction Protocols" 3rd edition. Site-specific DNA photoaffinity labeling of RNA polymerase III transcription complexes.
5. Chatterjee, N., Sen, P. and Bartholomew, B. (2008) “The SWI/SNF and RSC Nucleosome Remodeling Complexes” in Handbook of Cell Signaling, Publisher Elsevier Inc.
1. Hota, S.K. and B. Bartholomew, (2011) Biochim. Biophys. Acta, Diversity of operation in ATP-dependent chromatin remodelers.
2. Prasad, P and B. Bartholomew (2010) Epigenetics 5(4), Control of nucleosome movement – to space or not to space nucleosomes?
3. Gangaraju, VK and Bartholomew, B (2007) Mutat. Res. 618, 3-17. Mechanisms of ATP dependent chromatin remodeling.
Biochemistry and Molecular Biology
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