Penn Veterinary Medicine | University of Pennsylvania

Description of Research Expertise

Research Interests

Control of Gene Expression, development, and oncogenesis.

Key words: Transcription, Development, Differentiation, Polycomb, B cell, Immunoglobulin, Oncogenesis.

Research Summary

The Atchison laboratory is interested in determining the molecular mechanisms responsible for transcriptional regulation and the control of differentiation. To pursue these studies, we explore the functions of a number of transcription factors that regulate immunoglobulin gene expression and that play important roles in lineage differentiation, embryonic development, or oncogenesis. These transcription factors include PU.1, IRF-4, E47, Pax-5, Oct4, STAT5, and YY1. Each of these proteins is crucial for either proper B cell, myeloid or erythroid development, or for embryonic development. Some are also involved in the process of somatic hypermutation of rearranged immunoglobulin genes. We pursue our studies by biochemical, molecular biological, genetic, and developmental approaches using a variety of experimental systems including cell lines representing defined stages of B cell development, multipotential tumor lines, transgenic animals, and chimeric mice. In addition to the above mammalian systems, some projects utilize Drosophila systems.

1. Function of the transcription factor YY1 as a Polycomb-group protein in transcriptional repression and embryonic development. We found that human YY1 can function as a Polycomb protein in vivo to repress transcription and to control embryonic development. YY1 also recruits other PcG proteins to DNA resulting in specific histone post-translational modifications.

2. Developmental control of transcription at the immunogloblulin kappa locus. Using chromatin immunoprecipitation (ChIP) assays, transfections, and knock-down approaches we are determining the developmental changes that occur at the kappa locus. Function of the specific transcription factors that control enhancer activity and locus accessibility are being explored.

3. Mechanism of recruitment to DNA of proteins needed for immunoglobulin somatic hypermutation. The role of enhancer binding proteins in the recruitment of AID and RPA to specific locations in the genome is being explored.

4. Function of Oct4 in transcription and development. We are using molecular biochemical and knock-in approaches to study the function of this transcription factor that is crucial for stem cell pluripotency.

5. Role of transcription factor Pax-5 in hematopoietic development and oncogenesis. We are studying the function of Pax5 in controlling the commitment to the B cell lineage compared to the myeloid lineage. In addition, we are examining the function of Pax5 in oncogenesis in association with c-myc.


Rotation projects for 2006-2007

1. How does STAT5 control Ig? gene expression in early B cell development?
2. How do transcription factors recruit somatic hypermutation machinery to the rearranged immunoglobulin V gene?
3. What is the function of the YY1 REPO domain in PcG DNA recruitment, transcriptional repression, and B cell function?
4. How does sumoylation affect transcription factor function?
5. How do competitive interactions between transcription factors control gene expression?


Lab personnel:

Michael Atchison, Ph.D. P.I.
Dr. Atchison tries to work in the lab, and on occasion, actually succeeds. Recent projects include the function of YY1 in developing organisms and the role of enhancer binding factors in somatic hypermutation.

Kyoungsook Park, Ph.D. Visiting Scientist
Dr. Park is studying subcellular localization of CtBP and YY1, and the role of proteins sumoylation in these processes. She is also studying developmentally controlled transcription factor binding at the Ig kappa locus.

Frank Wilkinson, Ph.D. Post-doc
Dr. Wilkinson is studying interaction of YY1 with other PcG proteins. He is also using transgenic approaches to define specific YY1 regions needed for specific molecular functions.

Arindam Basu, Ph.D. Post-doc
Dr. Basu is studying transcriptional control mechanisms.

Fang Wei, Ph.D Post-doc
Dr. Wei is exploring the function of transcription factor Oct4 in embryonic stem cells and the function of YY1 and Pax5 in immunoglobulin locus contraction.

Christina Zaprazna, M.S. Graduate Student
Ms. Zaprazna is exploring the mechanism of transcription factor recruitment to DNA of enzymes needed for somatic hypermutation of immunoglobulin V regions.

Xuan Pan, VMD-PhD Student
Ms. Pan is studying the function of the REPO domain in transcription factor YY1 by biochemical, transfection, and transgenic approaches.

Suchita Hodawadekar, B.S. Research Specialist
Ms. Hodawadekar is studying developmental alterations in chromatin structure at the mouse Ig locus using chromatin immunoprecipitation assays. She is also is studying the role of STAT5 in controlling Ig kappa locus activity.

Aisha Ghias, Research Specialist
Ms. Ghias is studying the protein complexes that bind to the Ig kappa enhancers.

Brandan Youngman, Undergraduate student
Mr. Youngman is studying the mechanisms of PcG protein interactions by GST-pull down assays.

Danika Perry, Research Specialist
Ms. Perry is studying function of transcription factor YY1 by transgenic approaches.

Selected Publications

Hodawadekar, Suchita. Yu, Duonan. Cozma, Diana. Freedman, Bruce. Sunyer, Oriol. Atchison, Michael L. Thomas-Tikhonenko, Andrei.: B-Lymphoma cells with epigenetic silencing of Pax5 trans-differentiate into macrophages, but not other hematopoietic lineages. Experimental Cell Research 313(2): 331-40, Jan 15 2007.

Wei, Fang. Scholer, Hans R. Atchison, Michael L.: Sumoylation of Oct4 enhances its stability, DNA binding, and transactivation. Journal of Biological Chemistry 282(29): 21551-60, Jul 20 2007.

Hodawadekar, Suchita. Wei, Fang. Yu, Duonan. Thomas-Tikhonenko, Andrei. Atchison, Michael L.: Epigenetic histone modifications do not control Igkappa locus contraction and intranuclear localization in cells with dual B cell-macrophage potential. Journal of Immunology 177(9): 6165-71, Nov 1 2006.

Wilkinson, Frank H. Park, Kyoungsook. Atchison, Michael L.: Polycomb recruitment to DNA in vivo by the YY1 REPO domain. Proceedings of the National Academy of Sciences of the United States of America 103(51): 19296-301, Dec 19 2006.

Bai, Y, Srinivasan, L., Perkins, L., and Atchison, M. L.: Acetylation regulates the Ig?3’ enhancer through two distinct mechanisms J. Immunol 175: 5160-5169, 2005.

Srinivasan, Lakshmi. Pan, Xuan. Atchison, Michael L.: Transient requirements of YY1 expression for PcG transcriptional repression and phenotypic rescue. Journal of Cellular Biochemistry 96(4): 689-99, Nov 1 2005.

McDevit, Daniel C. Perkins, Leslie. Atchison, Michael L. Nikolajczyk, Barbara S.: The Ig kappa 3' enhancer is activated by gradients of chromatin accessibility and protein association. Journal of Immunology 174(5): 2834-42, Mar 1 2005.

Bai, Yuchen. Srinivasan, Lakshmi. Perkins, Leslie. Atchison, Michael L.: Protein acetylation regulates both PU.1 transactivation and Ig kappa 3' enhancer activity. Journal of Immunology 175(8): 5160-9, Oct 15 2005.

Atchison, Michael.: VMSTP Combined Degree Training (VMD/PhD): key features of the program at the University of Pennsylvania. Journal of Veterinary Medical Education 32(3): 337-41, 2005.

Atchison, L., Ghias, A., Wilkinson, F., Bonini, N., and Atchison, M.L.: Transcription factor YY1 functions as a PcG in vivo. EMBO J. 22: 1347-1358 , 2003.

Yu, D., Allman, D., Goldschmidt, M.H., Atchison, M.L., Monroe, J.G., and Thomas-Tikhonenko, A. : Oscillation between B-lymphoid and myeloid lineages in Myc-induced hematopoietic tumors following spontaneous silencing/reactivation of the EBF/Pax5 pathway. Blood 101: 1950-1955, 2003.

Nagualapalli, S., Goheer, A., Pitt, L., McIntosh, L.P., and Atchison, M.L.: Mechanism of E47-Pip interaction on DNA resulting in transcriptional synergy and activation of immunoglobulin germline sterile transcripts. Mol. Cell Biol. 22: 7337-7350 , 2002.

Hong, W., Kim, A.Y., Ky, S., Rakowski, C., Seo, S.-B., Chakravarti, D., Atchison, M., and Blobel, G.A.: Inhibition of CBP-mediated protein acetylation by the Ets family oncoprotein PU.1. Mol. Cell Biol. 22: 3729-3743 , 2002.

Maitra, S. and Atchison, M.L.: BSAP can repress enhancer activity by targeting PU.1 function. Mol. Cell Biol. 20: 1911-1922, 2000.

McDevit, D.C., Perkins, L., Atchison, M.L., and Nikolajczyk, B.S.: The Ig?3’ enhancer is activated by gradients of chromatin accessibility and protein association J. Immunol 174: 2834-2842 , 2005.

Srinivasan, Lakshmi. Atchison, Michael L.: YY1 DNA binding and PcG recruitment requires CtBP. Genes & Development 18(21): 2596-601, Nov 1 2004.

Boopathi, Ettickan. Lenka, Nibedita. Prabu, Subbuswamy K. Fang, Ji-Kang. Wilkinson, Frank. Atchison, Michael. Giallongo, Agata. Avadhani, Narayan G.: Regulation of murine cytochrome c oxidase Vb gene expression during myogenesis: YY-1 and heterogeneous nuclear ribonucleoprotein D-like protein (JKTBP1) reciprocally regulate transcription activity by physical interaction with the BERF-1/ZBP-89 factor. Journal of Biological Chemistry 279(34): 35242-54, Aug 20 2004.

Joo, Myungsoo. Park, Gye Young. Wright, Jeffrey G. Blackwell, Timothy S. Atchison, Michael L. Christman, John W.: Transcriptional regulation of the cyclooxygenase-2 gene in macrophages by PU.1. Journal of Biological Chemistry 279(8): 6658-65, Feb 20 2004.

Atchison, Lakshmi. Ghias, Ayesha. Wilkinson, Frank. Bonini, Nancy. Atchison, Michael L.: Transcription factor YY1 functions as a PcG protein in vivo. EMBO Journal 22(6): 1347-58, Mar 17 2003.

Yu, Duonan. Allman, David. Goldschmidt, Michael H. Atchison, Michael L. Monroe, John G. Thomas-Tikhonenko, Andrei.: Oscillation between B-lymphoid and myeloid lineages in Myc-induced hematopoietic tumors following spontaneous silencing/reactivation of the EBF/Pax5 pathway. Blood 101(5): 1950-5, Mar 1 2003.

Pongubala, J M. Van Beveren, C. Nagulapalli, S. Klemsz, M J. McKercher, S R. Maki, R A. Atchison, M L.: Effect of PU.1 phosphorylation on interaction with NF-EM5 and transcriptional activation. Science 259(5101): 1622-5, Mar 12 1993.

Nagulapalli, Sujatha. Goheer, Aisha. Pitt, Leslie. McIntosh, Lawrence P. Atchison, Michael L.: Mechanism of e47-Pip interaction on DNA resulting in transcriptional synergy and activation of immunoglobulin germ line sterile transcripts. Molecular & Cellular Biology 22(20): 7337-50, Oct 2002.

Marecki, S. Atchison, M L. Fenton, M J.: Differential expression and distinct functions of IFN regulatory factor 4 and IFN consensus sequence binding protein in macrophages. Journal of Immunology 163(5): 2713-22, Sep 1 1999.

Meraro, D. Hashmueli, S. Koren, B. Azriel, A. Oumard, A. Kirchhoff, S. Hauser, H. Nagulapalli, S. Atchison, M L. Levi, B Z.: Protein-protein and DNA-protein interactions affect the activity of lymphoid-specific IFN regulatory factors. Journal of Immunology 163(12): 6468-78, Dec 15 1999.

Nagulapalli, S. Atchison, M L.: Transcription factor Pip can enhance DNA binding by E47, leading to transcriptional synergy involving multiple protein domains. Molecular & Cellular Biology 18(8): 4639-50, Aug 1998.

Fisher, R C. Olson, M C. Pongubala, J M. Perkel, J M. Atchison, M L. Scott, E W. Simon, M C.: Normal myeloid development requires both the glutamine-rich transactivation domain and the PEST region of transcription factor PU.1 but not the potent acidic transactivation domain. Molecular & Cellular Biology 18(7): 4347-57, Jul 1998.

Perkel, J M. Atchison, M L.: A two-step mechanism for recruitment of Pip by PU.1. Journal of Immunology 160(1): 241-52, Jan 1 1998.

McNeil, S. Guo, B. Stein, J L. Lian, J B. Bushmeyer, S. Seto, E. Atchison, M L. Penman, S. van Wijnen, A J. Stein, G S.: Targeting of the YY1 transcription factor to the nucleolus and the nuclear matrix in situ: the C-terminus is a principal determinant for nuclear trafficking. Journal of Cellular Biochemistry 68(4): 500-10, Mar 15 1998.

Bushmeyer, S M. Atchison, M L.: Identification of YY1 sequences necessary for association with the nuclear matrix and for transcriptional repression functions. Journal of Cellular Biochemistry 68(4): 484-99, Mar 15 1998.

Zhang, C. Gadue, P. Scott, E. Atchison, M. Poncz, M.: Activation of the megakaryocyte-specific gene platelet basic protein (PBP) by the Ets family factor PU.1. Journal of Biological Chemistry 272(42): 26236-46, Oct 17 1997.

Pongubala, J M. Atchison, M L.: PU.1 can participate in an active enhancer complex without its transcriptional activation domain. Proceedings of the National Academy of Sciences of the United States of America 94(1): 127-32, Jan 7 1997.

Costa, M W. Atchison, M L.: Identification of an Spl-like element within the immunoglobulin kappa 3' enhancer necessary for maximal enhancer activity. Biochemistry 35(26): 8662-9, Jul 2 1996.

Bushmeyer, S. Park, K. Atchison, M L.: Characterization of functional domains within the multifunctional transcription factor, YY1. Journal of Biological Chemistry 270(50): 30213-20, Dec 15 1995.

Nagulapalli, S. Pongubala, J M. Atchison, M L.: Multiple proteins physically interact with PU.1. Transcriptional synergy with NF-IL6 beta (C/EBP delta, CRP3). Journal of Immunology 155(9): 4330-8, Nov 1 1995.

Atchison, L. Atchison, M L. Cannizzaro, L A.: High-resolution mapping of 10 unique DNA sequences to human chromosome 3 subregions by in situ hybridization. Cytogenetics & Cell Genetics 71(2): 136-8, 1995.

Pongubala, J M. Atchison, M L.: Activating transcription factor 1 and cyclic AMP response element modulator can modulate the activity of the immunoglobulin kappa 3' enhancer. Journal of Biological Chemistry 270(17): 10304-13, Apr 28 1995.

Atchison, L. Comis, R L. Atchison, M L.: Construction of rare restriction site (NotI, SacII and ClaI) linking libraries and sequence-tagged site analysis of single-copy clones from a human chromosome-3-specific library. Gene 151(1-2): 325-8, Dec 30 1994.

Atchison, L. Comis, R L. Atchison, M L.: Construction of human chromosome-3-specific radiation hybrids and characterization by Alu-PCR. Gene 151(1-2): 321-4, Dec 30 1994.

Satyamoorthy, K. Park, K. Atchison, M L. Howe, C C.: The intracisternal A-particle upstream element interacts with transcription factor YY1 to activate transcription: pleiotropic effects of YY1 on distinct DNA promoter elements. Molecular & Cellular Biology 13(11): 6621-8, Nov 1993.

Basu, A. Park, K. Atchison, M L. Carter, R S. Avadhani, N G.: Identification of a transcriptional initiator element in the cytochrome c oxidase subunit Vb promoter which binds to transcription factors NF-E1 (YY-1, delta) and Sp1. Journal of Biological Chemistry 268(6): 4188-96, Feb 25 1993.

Gualberto, A. LePage, D. Pons, G. Mader, S L. Park, K. Atchison, M L. Walsh, K.: Functional antagonism between YY1 and the serum response factor. Molecular & Cellular Biology 12(9): 4209-14, Sep 1992.

Pongubala, J M. Nagulapalli, S. Klemsz, M J. McKercher, S R. Maki, R A. Atchison, M L.: PU.1 recruits a second nuclear factor to a site important for immunoglobulin kappa 3' enhancer activity. Molecular & Cellular Biology 12(1): 368-78, Jan 1992.

Park, K. Atchison, M L.: Isolation of a candidate repressor/activator, NF-E1 (YY-1, delta), that binds to the immunoglobulin kappa 3' enhancer and the immunoglobulin heavy-chain mu E1 site. Proceedings of the National Academy of Sciences of the United States of America 88(21): 9804-8, Nov 1 1991.

Pongubala, J M. Atchison, M L.: Functional characterization of the developmentally controlled immunoglobulin kappa 3' enhancer: regulation by Id, a repressor of helix-loop-helix transcription factors. Molecular & Cellular Biology 11(2): 1040-7, Feb 1991.

Atchison, M L. Delmas, V. Perry, R P.: A novel upstream element compensates for an ineffectual octamer motif in an immunoglobulin V kappa promoter. EMBO Journal 9(10): 3109-17, Oct 1990.

Atchison, L. Cannizzaro, L. Caamano, J. Atchison, M. Comis, R L.: Assignment of 35 single-copy and 17 repetitive sequence DNA probes to human chromosome 3: high-resolution physical mapping of 7 DNA probes by in situ hybridization. Genomics 6(3): 441-50, Mar 1990.

Atchison, M L. Meyuhas, O. Perry, R P.: Localization of transcriptional regulatory elements and nuclear factor binding sites in mouse ribosomal protein gene rpL32. Molecular & Cellular Biology 9(5): 2067-74, May 1989.

Perry, R P. Atchison, M L. Kelley, D E. Peterson, M L.: Transcriptional and processing-level control of immunoglobulin gene expression. [Review] [13 refs] Annals of the New York Academy of Sciences 546: 25-33, 1988.

Atchison, M L. Perry, R P.: Complementation between two cell lines lacking kappa enhancer activity: implications for the developmental control of immunoglobulin transcription. EMBO Journal 7(13): 4213-20, Dec 20 1988.

Atchison, M L.: Enhancers: mechanisms of action and cell specificity. [Review] [164 refs] Annual Review of Cell Biology 4: 127-53, 1988.

Kelley, D E. Pollok, B A. Atchison, M L. Perry, R P.: The coupling between enhancer activity and hypomethylation of kappa immunoglobulin genes is developmentally regulated. Molecular & Cellular Biology 8(2): 930-7, Feb 1988.

Atchison, M L. Perry, R P.: The role of the kappa enhancer and its binding factor NF-kappa B in the developmental regulation of kappa gene transcription. Cell 48(1): 121-8, Jan 16 1987.

Friedberg, T. Waxman, D J. Atchison, M. Kumar, A. Haaparanta, T. Raphael, C. Adesnik, M.: Isolation and characterization of cDNA clones for cytochromes P-450 immunochemically related to rat hepatic P-450 form PB-1. Biochemistry 25(24): 7975-83, Dec 2 1986.

Atchison, M L. Perry, R P.: Tandem kappa immunoglobulin promoters are equally active in the presence of the kappa enhancer: implications for models of enhancer function. Cell 46(2): 253-62, Jul 18 1986.

Atchison, M. Adesnik, M.: Gene conversion in a cytochrome P-450 gene family. Proceedings of the National Academy of Sciences of the United States of America 83(8): 2300-4, Apr 1986.

Mentaberry, A. Adesnik, M. Atchison, M. Norgard, E M. Alvarez, F. Sabatini, D D. Colman, D R.: Small basic proteins of myelin from central and peripheral nervous systems are encoded by the same gene. Proceedings of the National Academy of Sciences of the United States of America 83(4): 1111-4, Feb 1986.

Adesnik, M. Atchison, M.: Genes for cytochrome P-450 and their regulation. [Review] [244 refs] CRC Critical Reviews in Biochemistry 19(3): 247-305, 1986.

Atchison, M. Atchison, M L. Van Duuren, B L.: Cocarcinogenesis in vitro using Balb/3T3 cells and aromatic hydrocarbon cocarcinogens. Cell Biology & Toxicology 1(4): 323-31, Oct 1985.

Atchison, M. Adesnik, M.: A cytochrome P-450 multigene family. Characterization of a gene activated by phenobarbital administration. Journal of Biological Chemistry 258(18): 11285-95, Sep 25 1983.

Kimelberg, H K. Atchison, M L.: Effects of entrapment in liposomes on the distribution, degradation and effectiveness of methotrexate in vivo. Annals of the New York Academy of Sciences 308: 395-410, 1978.