Blaine Bartholomew, Ph.D.
Department of Epigenetics and Molecular Carcinogenesis, Division of VP, Research
Present Title & Affiliation
Professor, Department of Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX
My research interest is on the structure and function of ATP-dependent chromatin remodeling complexes and their mechanisms of nucleosome mobilization and reorganization. Given the size and complexity of these complexes, it has been essential for my lab to work on approaches for studying the physical interactions of remodelers with their nucleosomal substrates. I have taken a chemical biology type approach and have applied targeted protein and DNA modifications to map specific protein-protein and protein-DNA contacts. The reporters tethered to specific target sites have been of the photochemical, proteolytic, and fluorescent types. My lab uses Saccharomyces cerevisiae as our model system because once a particular contact has been found and mapped, we have been able to mutate that region in the protein and find the in vivo effects of these mutations on chromatin structure and function as well as the effects on its biochemical activity in vitro.
I am applying related approaches to examine changes in nucleosome structure when remodeled and have developed an approach for monitoring the interactions of several locations in the histone octamer with nucleosomal DNA. My lab is expanding and improving this technique to obtain more information about temporal changes in nucleosome structure. I am also interested in using single molecule approaches to examine nucleosome remodeling and have been involved in two collaborations to use single molecule Fluorescence Resonance Energy Transfer and DNA methylation accessibility with bisulfite sequencing to examine SWI/SNF and ISW2 remodeling. I am interested in finding the roles of histone modifications such as acetylation and methylation in the recruitment and regulation of the chromatin remodeler. I am also involved in studying the interplay of histone chaperones with ATP-dependent chromatin remodelers.
Education & Training
|1988||University of California, Davis, Davis, CA, USA, PHD, Chemistry|
|1982||Brigham Young University, Provo, UT, USA, BS, Chemistry|
- Hada A, Hota SK, Luo J, Lin YC, Kale S, Shaytan AK, Bhardwaj SK, Persinger J, Ranish J, Panchenko AR, Bartholomew B. Histone Octamer Structure Is Altered Early in ISW2 AT-Dependent Nucleosome Remodeling. Cell Rep 28(1):282-294.e6, 2019. PMID: 31269447.
- Brahma S, Ngubo M, Paul S, Udugama M, Bartholomew B. The Arp8 and Arp4 module acts as a DNA sensor controlling INO80 chromatin remodeling. Nat Commun 9(1):3309, 2018. e-Pub 2018. PMID: 30120252.
- Brahma S, Udugama MI, Kim J, Hada A, Bhardwaj SK, Hailu SG, Lee TH, Bartholomew B. INO80 exchanges H2A.Z for H2A by translocating on DNA proximal to histone dimers. Nat Commun 8:15616, 2017. e-Pub 2017. PMID: 28604691.
- Sen P, Luo J, Hada A, Hailu SG, Dechassa ML, Persinger J, Brahma S, Paul S, Ranish J, Bartholomew B. Loss of Snf5 Induces Formation of an Aberrant SWI/SNF Complex. Cell Rep 18(9):2135-2147, 2017. PMID: 28249160.
- Prasad R, D'Arcy S, Hada A, Luger K, Bartholomew B. Coordinated action of Nap1 and RSC in disassembly of tandem nucleosomes. Mol Cell Biol 36(17):2262-71, 2016. e-Pub 2016. PMID: 27273866.
- Harada BT, Hwang WL, Deindl S, Chatterjee N, Bartholomew B, Zhuang X. Stepwise nucleosome translocation by RSC remodeling complexes. Elife 5, 2016. e-Pub 2016. PMID: 26895087.
- Creamer KM, Job G, Shanker S, Neale GA, Lin YC, Bartholomew B , Partridge JF. The Mi-2 Homolog Mit1 Actively Positions Nucleosomes within Heterochromatin To Suppress Transcription. Mol Cell Biol 34(11):2046-61, 2014. e-Pub 2014. PMID: 24662054.
- Bartholomew B. Monomeric actin required for INO80 remodeling. Nat Struct Mol Biol 20(4):405-7, 2013. PMID: 23552289.
- Hota SK, Bhardwaj SK, Deindl S, Lin YC, Zhuang X, Bartholomew B. Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains. Nat Struct Mol Biol 20(2):222-9, 2013. e-Pub 2013. PMID: 23334290.
- Sen P, Vivas P, Dechassa ML, Mooney AM, Poirier MG, Bartholomew B. The SnAC domain of SWI/SNF is a histone anchor required for remodeling. Mol Cell Biol 33(2):360-70, 2013. e-Pub 2012. PMID: 23149935.
- Deindl S, Hwang WL, Hota SK, Blosser TR, Prasad P, Bartholomew B, Zhuang X. ISWI remodelers slide nucleosomes with coordinated multi-base-pair entry steps and single-base-pair exit steps. Cell 152(3):442-52, 2013. PMID: 23374341.
- Dechassa ML, Hota SK, Sen P, Chatterjee N, Prasad P, Bartholomew B. Disparity in the DNA translocase domains of SWI/SNF and ISW2. Nucleic Acids Res 40(10):4412-21, 2012. e-Pub 2012. PMID: 22298509.
- Hota SK, Bartholomew B. Approaches for studying nucleosome movement by ATP-dependent chromatin remodeling complexes. Methods Mol Biol 809:367-80, 2012. PMID: 22113289.
- Hota SK, Dechassa ML, Prasad P, Bartholomew B. Mapping protein-DNA and protein-protein interactions of ATP-dependent chromatin remodelers. Methods Mol Biol 809:381-409, 2012. PMID: 22113290.
- Darst RP, Pardo CE, Pondugula S, Gangaraju VK, Nabilsi NH, Bartholomew B, Kladde MP. Simultaneous single-molecule detection of endogenous C-5 DNA methylation and chromatin accessibility using MAPit. Methods Mol Biol 833:125-41, 2012. PMID: 22183592.
- Paul S, Bartholomew B. Regulation of ATP-dependent chromatin remodelers: Accelerators/Brakes, Anchors and Sensors. Biochem Soc Trans 46(6):1423-1430, 2018. e-Pub 2018. PMID: 30467122.
- Meng H, Bartholomew B. Emerging Roles of Transcriptional Enhancers In Chromatin Looping And Promoter-Proximal Pausing Of RNA Polymerase II. J Biol Chem 293(36):13786-13794, 2018. e-Pub 2017. PMID: 29187597.
- Bartholomew B. Proteasomes beyond proteolysis: Roles in heterochromatin maintenance. J Biol Chem 292(41):17156-17157, 2017. PMID: 29030538.
- Bartholomew B. ISWI chromatin remodeling: one primary actor or a coordinated effort?. Curr Opin Struct Biol 24:150-5, 2014. e-Pub 2014. PMID: 24561830.
- Bartholomew B. Regulating the Chromatin Landscape: Structural and Mechanistic Perspectives. Annu Rev Biochem 83:671-96, 2014. e-Pub 2014. PMID: 24606138.