Claims
- 1. A method for identifying a compound that alters higher order chromatin dependent chromosome stability in mitosis and meiosis, said method comprising incubating a substrate for a methyltransferase, in the presence of a methyl donor, with a methyltransferase with Suv39h-like methyltransferase activity, in the presence or absence of a test compound and determining whether the compound modulates the methyltransferase activity.
- 2. The method of claim 1, wherein the methyltransferase with Suv39h-like activity methylates histone H3 at lysine 9.
- 3. The method of claim 2, wherein the methyltransferase with Suv39h-like activity is murine Suv39h1 or human SUV39H1.
- 4. The method of claim 2, wherein the methyltransferase with Suv39h-like activity is murine Suv39h2 or human SUV39H2.
- 5. The method of any one of claims 1 to 4, wherein the substrate is histone H3 or an N-terminal fragment thereof that contains the methylation site at lysine 9.
- 6. The method of claim 5, wherein the histone H3 N-terminal fragment has the amino acid sequence as set forth in SEQ ID NO:7.
- 7. The method of any one of claims 1 to 6, wherein the methyl donor is methionine or S-adenosyl-L-methionine.
- 8. The method of any one of claims 1 to 7, wherein the methyl group of the methyl donor carries a detectable label.
- 9. The method of claim 8, wherein the methyl donor carries a chromogenic label and the methyltransferase activity is determined by measuring the change in colour upon transfer of the methyl group to the substrate.
- 10. The method of claim 8, wherein the methyl donor carries a radioactive label and the methyltransferase activity is determined by measuring the radioactivity transferred to the substrate upon transfer of the methyl group.
- 11. The method of any one of claims 1 to 7, wherein the methyltransferase activity is determined immunologically by quantifying the binding of an antibody specific for the methylation site of the substrate.
- 12. The method of claim 11 wherein the substrate carries a detectable label.
- 13. An antibody that specifically recognises methylated lysine 9 in histone H3.
- 14. The use of the H3-K9 methyl-specific antibody of claim 13 for diagnosis of a human disease associated with aberrant gene expression and genomic instability through chromosome mis-segregation.
- 15. A compound identified in a method defined in any one of claims 1 to 12 for use in the the therapy of cancer.
- 16. A compound identified in a method defined in any one of claims 1 to 12 for contraception.
- 17. The compound of claim 15 for use in temporary male conception.
Priority Claims (2)
Number |
Date |
Country |
Kind |
EP 00 112 345.4 |
Jun 2000 |
EP |
|
EP 00 112 479.1 |
Jun 2000 |
EP |
|
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority benefit of U.S. Provisional Application No. 60/224,220, filed Aug. 9, 2000, which is hereby incorporated by reference in its entirety.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60224220 |
Aug 2000 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09876221 |
Jun 2001 |
US |
Child |
10323968 |
Dec 2002 |
US |