Analysis of the DNA binding and transcriptional activation properties of the Ets1 oncoprotein
A Gegonne1, B Punyammalee, B Rabault
1Laboratoire d'Oncologie Virale et Cellulaire, CNRS URA 1443, Centre Universitaire, Orsay, France.
Abstract:
The c-ets1 gene product (Ets1) is the prototype of a family of sequence-specific transcriptional activators which have been implicated in various developmental processes and in the response of cells to a variety of extracellular stimuli. We report here a structure-function analysis of the DNA binding and transcriptional activation properties of Ets1. The minimal region required for specific DNA binding is located at the carboxy-terminus of Ets1, a domain highly conserved in all known members of the Ets family. Transcriptional activation by Ets1 in mammalian cells requires an additional domain of 110 amino acids characterized by a high content of acidic residues and localized in the amino-terminal half of the protein. This domain also functions as a transcriptional activation domain in yeast cells when linked to the heterologous DNA binding domain of Gal4. In contrast to its conservation in Ets1 proteins across vertebrate species, this activation domain is not conserved in other members of the Ets family. These results indicate that an important level of specificity between different members of the Ets family may reside in the differential interactions of their respective activation domains with distinct general transcription factors or different associated coactivators.
Insights
The Ets1 protein
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- The Ets1 protein is a key transcriptional activator involved in development and cellular responses.
- Understanding Ets1's structure-function is crucial for deciphering gene regulation.
Purpose of the Study:
- To analyze the DNA binding and transcriptional activation properties of Ets1.
- To identify the specific domains responsible for Ets1's function.
Main Methods:
- Structure-function analysis of the Ets1 protein.
- Assessing DNA binding and transcriptional activation in mammalian and yeast cells.
Main Results:
- The DNA binding domain of Ets1 is at its carboxy-terminus and is highly conserved.
- A distinct amino-terminal domain mediates transcriptional activation in mammalian cells.
- This activation domain is not conserved in other Ets family members.
Conclusions:
- Ets1's DNA binding and activation domains have distinct functional roles.
- Differential activation domains contribute to the specificity of Ets family members.
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