Title

Regulation of Genes by ETS Transcription Factors

Type of Submission

Poster

Keywords

ETS, transcription, chromatin, cancer, gene expression

Abstract

The interaction of growth factors with their receptors triggers a cascade of intracellular signals which can result in the activation or repression of various genes. The variation in gene expression ultimately gives rise to diverse biological effects such as differentiation and proliferation. Aberrant expression of these genes often leads to cancer. Our lab focuses on a signal transduction pathway that is downstream of Ras which is one of the most frequently activated oncogenes in human cancer. Growth factors bind to their cognate tyrosine kinase receptors which ultimately lead to the activation of Ras. Activated Ras leads to the activation of one well characterized downstream effecter pathway of Ras – the Raf/Mek/Map Kinase pathway. Once Map Kinase is activated it translocates to the nuclease and regulates transcription factors via phosphorylation.

One well known target of Map Kinase, particularly Ets-2, is a member of the ETS families of transcription factors. These transcription factors have been linked to tumor progression in several types of cancers. They regulate the expression of genes that play a role in the regulation of cell cycle, apoptosis, extracellular matrix remodeling, and cell migration. Therefore, ETS transcription factors are thought to play a key role in tumor invasion and metastasis.

Phosphorylation of Ets-2 leads to the expression of known target genes such as c-myc, MMP-9 and miR17-92. One way that transcription factors exert their effects are by altering the chromatin environment. Two key mechanisms for altering chromatin structure are by chromatin remodeling complexes and histone modification enzymes. Ets-2 is known to interact with different subunits of both remodeling and modification proteins. However it is unknown what the outcome of this interaction is. We have hypothesized that the interaction of ETS-2 with CBP, (a well-known histone acetyltransferase) leads to an increased acetylation of histones which leads to the expression of target genes. We are investigating this by performing ChIP (chromatin immunoprecipitation) analysis.

Faculty Sponsor or Advisor’s Name

Alicia Schaffner

Campus Venue

Stevens Student Center

Location

Cedarville, OH

Start Date

4-16-2014 11:00 AM

End Date

4-16-2014 2:00 PM

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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Apr 16th, 11:00 AM Apr 16th, 2:00 PM

Regulation of Genes by ETS Transcription Factors

Cedarville, OH

The interaction of growth factors with their receptors triggers a cascade of intracellular signals which can result in the activation or repression of various genes. The variation in gene expression ultimately gives rise to diverse biological effects such as differentiation and proliferation. Aberrant expression of these genes often leads to cancer. Our lab focuses on a signal transduction pathway that is downstream of Ras which is one of the most frequently activated oncogenes in human cancer. Growth factors bind to their cognate tyrosine kinase receptors which ultimately lead to the activation of Ras. Activated Ras leads to the activation of one well characterized downstream effecter pathway of Ras – the Raf/Mek/Map Kinase pathway. Once Map Kinase is activated it translocates to the nuclease and regulates transcription factors via phosphorylation.

One well known target of Map Kinase, particularly Ets-2, is a member of the ETS families of transcription factors. These transcription factors have been linked to tumor progression in several types of cancers. They regulate the expression of genes that play a role in the regulation of cell cycle, apoptosis, extracellular matrix remodeling, and cell migration. Therefore, ETS transcription factors are thought to play a key role in tumor invasion and metastasis.

Phosphorylation of Ets-2 leads to the expression of known target genes such as c-myc, MMP-9 and miR17-92. One way that transcription factors exert their effects are by altering the chromatin environment. Two key mechanisms for altering chromatin structure are by chromatin remodeling complexes and histone modification enzymes. Ets-2 is known to interact with different subunits of both remodeling and modification proteins. However it is unknown what the outcome of this interaction is. We have hypothesized that the interaction of ETS-2 with CBP, (a well-known histone acetyltransferase) leads to an increased acetylation of histones which leads to the expression of target genes. We are investigating this by performing ChIP (chromatin immunoprecipitation) analysis.