Synthetic transcriptional modulators and uses thereof
AssigneePresident and Fellows of Harvard College
InventorsGregory L. Verdine, Origene Nyanguile
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Abstract
Novel synthetic transcriptional modulators having at least one selected ligand linked to at least one transcriptional modulating portion are described. The transcriptional modulators of the present invention can include a ligand linked to a chemical moiety. These transcriptional modulators can be used to selectively control gene expression and to identify components of the transcriptional machinery.
Claims35
A method for modulating expression of a target gene in a cell, comprising:
- contacting a cell comprising (i) a genetic construct encoding a chimeric protein which comprises at least one ligand-binding domain and a DNA-binding domain which is heterologous thereto, wherein the ligand-binding domain binds to a selected ligand, and (ii) a target gene under the control of at least one transcriptional regulatory element which is recognized by the DNA-binding domain of the chimeric protein with a transcriptional modulator which comprises the selected ligand linked to a transcription modulating portion under conditions which allow transcription of the target gene, such that expression of the target gene is modulated.
The method of claim wherein the ligand-binding domain of the chimeric protein comprises between about 50 and 350 amino acids.
A method for modulating expression of a target gene in a cell, comprising:
- contacting a cell comprising a genetic construct encoding a chimeric protein which comprises at least one ligand-binding domain and a DNA-binding domain which is heterologous thereto, wherein the ligand-binding domain binds to a selected ligand and the DNA-binding domain binds to a target gene under the control of at least one transcriptional regulatory element which is recognized by the DNA-binding domain of the chimeric protein with a transcriptional modulator which comprises the selected ligand linked to a transcription modulating portion under conditions which allow transcription of the target gene, such that expression of the target gene is modulated.
Dependencies are inferred from the claim text.