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Michael
Atchison, Ph.D.
Professor,
Dept of Biochemistry
Director, VMD-PhD Program
Genetics
and Gene Regulation Program
Address
139 Rosenthal
3800 Spruce Street
Philadelphia . PA . 19104
Office tel.: 215 898-6428
Lab tel.: 215 898-6394
Fax: 215 573-5189
E-mail: atchison@vet.upenn.edu
Link(s)
VMD/PhD
Combined Degree program
Dr.
Atchison at the Vet School
Dr.
Atchison in the Immunology Graduate Group:
Education
SUNY at Albany, B.S. (Biology), 1977
New York University School of Medicine, Ph.D. (Cell and Molecular
Biology), 1983
Fox Chase Cancer Center, Postdoctoral Fellow (Molecular Biology),
1984-1988
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Research
Interests
- Control of Gene Expression, Development, Immunoglobulins,
and Oncogenesis.
Key words: Transcription, Development,
Differentiation, Polycomb, B cell, Immunoglobulin, Oncogenesis.
Search PubMed for articles
Description
of Research
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.
- 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.
- 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.
- 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.
- 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.
- 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.
Recent
Publications
Wilkinson, F.H. and Atchison, M.L. Polycomb
recruitment to DNA in vivo by the YY1 REPO domain. Proc.
Natl. Acad. Sci. USA 103:19296-19301 (2006).
Hodawadekar, S, Wei, F., Yu, D., Thomas-Tikhonenko,
A., and Atchison, M.L. Epigenetic histone modifications do
not control Ig? locus contraction and intranuclear localization
in cells with dual B cell-macrophage potential. J. Immunol.
177:6165-6171 (2006).
Calame, K. and Atchison, M. YY1 Helps to bring
loose ends together. Genes Dev. 21:1145-1152 (2007).
Wei, F., Scholer, H.R., and Atchison, M.L. Sumoylation
of Oct4 Can Enhance its Stability, DNA Binding, and Transactivation.
J. Biol. Chem. 282:21551-21560 (2007).
Cozma, D., Yu, D., Hodawadekar, S., Azvolinsky,
A., Grande, S., Tobias, J.W., Metzgar, M.H., Paterosn, J.,
Erikson, J., Marafioti, T., Monroe, J.G., Atchison, M.L.,
and Thomas-Tikhonenko, A. Pax5 promotes lymphomagenesis through
the stimulation of B-cell receptor signaling. J. Clinical
Investigation (2007, in press).
Lab
Rotation
Projects
- How does STAT5 control Ig? gene expression
in early B cell development?
- What is the role of YY1 in immunoglobulin
locus contraction?
- What is the function of the YY1 REPO domain
in PcG DNA recruitment, transcriptional repression, and
B cell function?
- How does sumoylation affect transcription
factor function?
- 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.
Frank Wilkinson, Ph.D. Visiting Scientist
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 the function of YY1 and CtBP in 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.
Daniell Rowles, Undergraduate student
Ms. Rowles is studying the mechanisms of YY1 PcG protein functions
by competitor peptide and RNAi approaches.
last updated 8/2007
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