Epigenetic silencing of tumor suppressor genes
AssigneeThe Salk Institute for Biological Studies
InventorsMichael Witcher, Beverly M. Emerson
Life of this patent
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Abstract
Provided are methods of identifying a compound that binds to or modulates an activity of a CTCF polypeptide or CTCF polypeptide complex. Also provided are methods of monitoring a cancer state of a cell by detecting a chromatin boundary proximal to a tumor suppressor gene of the cell and by monitoring the formation of a gene-specific CTCF polypeptide complex in the cell. In addition, methods of selecting a treatment or determining a prognosis for a cancer related disease are provided. Provided are recombinant cells comprising recombinant CTCF genes, recombinant cells comprising CTCF knock downs or knock outs, and recombinant laboratory animals comprising CTCF knock downs or knock outs.
Claims32
A method of identifying a compound that binds to or modulates an activity of a CTCF polypeptide or CTCF polypeptide complex, the method comprising:
- (a.) contacting a biological or biochemical sample comprising the polypeptide or complex with a test compound;
- and,
- (b.) detecting binding of the test compound to the polypeptide or complex, or modulation of the activity of the polypeptide or complex by the test compound, thereby identifying the compound that binds to or modulates the activity of the CTCF polypeptide or complex.
4-8. (canceled)
14-15. (canceled)
The method of claim 27, wherein the compound induces or potentiates the activity of the CTCF polypeptide or complex by promoting poly(ADP-ribosyl)ation of CTCF or by promoting poly(ADP-ribosylation) of a CTCF-associated cofactor.
(canceled)
(canceled)
A method of monitoring a cancer or age-related disease state of a cell, the method comprising detecting destabilization of a chromatin boundary proximal to a tumor suppressor gene of the cell, wherein destabilization of the chromatin boundary correlates with genomic instability or a tumorigenesis process in the cell.
33-40. (canceled)
A method of selecting a treatment or determining a prognosis for a cancer- or age-related disease, the method comprising:
- measuring CTCF protein or CTCF complex binding within or proximal to a gene in a patient, wherein CTCF protein or complex binding within or proximal to gene is correlated with disease progression, or treatment selection;
- and,
- providing a patient prognosis based upon said CTCF protein or complex binding, or
- selecting a treatment course based upon said CTCF protein or complex binding.
42-50. (canceled)
A recombinant cell, comprising:
- a recombinant gene comprising a gene encoding CTCF under the control of a heterologous promoter;
- and,
- a recombinant gene comprising a tumor suppressor promoter operably linked to a reporter.
52-61. (canceled)
Dependencies are inferred from the claim text.