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Michael A. Mancini
Baylor College of MedicineDepartment: Department of Molecular and Cellular BiologyAddress: One Baylor Plaza DeBakey Bldg. Rm. M803 Houston, Texas 77030 Phone: 713-798-8952 Fax: 713-798-3175 Email: mancini@bcm.edu Web: www.bcm.edu/mcb/?PMID=9330 |
Education
Ph.D., University of Texas Health Science Center at San Antonio
Postdoctoral, University of Texas Institute of Biotechnology
Honors
Research Topic
Transcriptional analyses at the single cell level
Research Description
Investigating the functional relationship(s) between dynamic nuclear organization and transcription is the principal interest of my laboratory. The recent ability to visualize transcription factor dynamics (e.g., using fluorescent fusion proteins and time-lapse digital imaging/photobleaching approaches; Figure 1) has provided new insight into molecular and cellular regulatory mechanisms. The familiar stick-figure drawings found in textbooks, showing factors bound "statically" to a promoter and/or each other, fail to adequately represent the complexity of transcription in living cells.
With these issues in mind, we have focused upon members of the nuclear receptor superfamily and their coregulators as a model system. We have found that estrogen and androgen receptors, and the p160 class coactivators, have a common dynamic association with specific nuclear subcompartments. Through the study of these transcription factors within a live context, it has become evident intranuclear organization and regulated dynamics can correlate with transcription function. Thus at a single cell level, within minutes of adding ligand, spatial and mobility characteristics can be defined long before transcription output is generally detectable.
We have recently developed new cell lines that further facilitate the study of transcription mechanisms (Figure 2), often at a very high throughput level using new instrumentation (thousands of pictures per hour). As a result, we now can perform multiplex transcription assays in single cells for the following:
a) nuclear-cytoplasmic translocation,
b) subnuclear localization patterns,
c) promoter array targeting (including protein-DNA dynamics),
d) promoter specific protein-protein interactions,
e) chromatin modeling (histone modifications and large-scale, condensation or decondensation)
f) transcription readout.
These advances should provide exciting opportunities for the future, especially when considering high throughput microscopy-based possibilities of library screening (compounds, cDNA's, siRNA's, monoclonal antibodies). Collectively, single cell approaches will foster investigations to explore the mechanistic interplay between intranuclear dynamics and the regulation of gene expression at heretofore unavailable degrees of spatio-temporal resolution.
Selected Publications
- Hinojos, C.A.D., Sharp, Z.D. and Mancini, M.A. (2005). Molecular dynamics and nuclear reception function. Trends Endocrinol. Metab. 16(1): 12-18.
- Sharp ZD, Stenoien DL, Mancini MG, Ouspenski II, Mancini, M.A. (2004) Inactivating Pit-1 mutations alter subnuclear dynamics suggesting a protein misfolding and nuclear stress response. J. Cell. Biochem. 92: 664-78.
- Dong, S., Stenoien, D.L., Qiu, J., Mancini, M.A. and Tweardy, D.J. (2004). Reduced intranuclear mobility of APL fusion proteins accompanies their mislocalization and results in sequestration and decreased mobility of retinoid X receptor alpha. Mol. Cell. Biol. 24: 4465-75.
- Contreras, A., Hale, T.K., Stenoien, D.L., Rosen, J.M., Mancini, M.A. and Herrera, R.E. (2003). The dynamic mobility of histone H1 is regulated by cyclin/CDK phosphorylation. Mol. Cell. Biol. 23: 8626-36.
- Stenoien, D.L., Mielke, M. and Mancini, M.A. (2002). Intranuclear ataxin1 inclusions contain both fast- and slow-exchanging components. Nat. Cell. Biol. 4: 806-10.
Lab Members
Current Graduate Students
Current Post Docs
Former Post Docs
Lab Photos
Last edited on: September 22, 2009