Click on Picture for Bio
Catharine Smith, Ph.D.
Tenure-Track Investigator
Signal Transduction Group
smithcat@exchange.nih.gov
| National Cancer Institute | Laboratory of Receptor Biology and Gene Expression | National Institutes of Health |
Click on Picture for Bio |
Catharine Smith, Ph.D. |
|---|
In the cell nucleus all genes are packaged into chromatin. The structure of chromatin can be quite complex given various levels of condensation. Our interest is in the mechanisms by which chromatin participates in transcriptional regulation particularly in response to signal transduction pathways. Our model system is the mouse mammary tumor virus (MMTV) promoter.
Transient transfection assays have been an invaluable tool to study transcriptional mechanisms. However, we have found that transfected promoter constructs are not always adequate models for their endogenous counterparts [reviewed in Smith and Hager, J Biol Chem 272: 27493-27497, 1997]. In the case of MMTV, transiently-transfected templates do not acquire ordered chromatin structure, probably because they do not replicate. When the MMTV promoter is incorporated into replicating chromatin in cells it adopts a very ordered structure with non-randomly positioned nucleosomes. These differences extend to the accessibility of transcription factors and nucleases to the promoter, the transfected MMTV template being much more accessible than the replicating template.
The differences in nucleoprotein structure cause the two MMTV templates to be regulated by distinct mechanisms. These regulatory differences have allowed us to characterize novel mechanisms by which chromatin structure influences gene expression. We have several projects ongoing which focus on regulation of the two MMTV templates by progesterone, cAMP signaling, or histone deacetylase (HDAC) inhibitors.
Regulation of the MMTV Promoter by cAMP Signaling
Repression of MMTV Transcription by Histone Deacetylase Inhibitors
Regulation of the MMTV Promoter by Progesterone Receptor
