SELECTIVE OXIDATION OF 5-METHYLCYTOSINE BY TET-FAMILY PROTEINS
First Claim
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1. A method of regulating a cellular fate of an adult cell that is isolated and purified, the method comprising:
- regulating a methylation status of one or more cytosine bases in the adult cell, wherein the regulating comprises contacting the adult cell that is isolated and purified with an effective amount of;
(i) an enzyme or fragment thereof that converts (a) 5-methylcytosine to 5-hydroxymethylcytosine, (b) 5-methylcytosine to an acid beyond hydroxymethlyation, or (c) 5-methylcytosine to an aldehyde beyond hydroxymethlyation;
(ii) an inhibitor that decreases or prevents hydroxymethylation;
or (iii) a combination thereof, andwherein the regulating the methylation status thereby modifies the cellular fate of the adult cell that is isolated and purified.
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Abstract
The present invention provides for novel methods for regulating and detecting the cytosine methylation status of DNA. The invention is based upon identification of a novel and surprising catalytic activity for the family of TET proteins, namely TET1, TET2, TET3, and CXXC4. The novel activity is related to the enzymes being capable of converting the cytosine nucleotide 5-methylcytosine into 5-hydroxymethylcytosine by hydroxylation.
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Citations
22 Claims
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1. A method of regulating a cellular fate of an adult cell that is isolated and purified, the method comprising:
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regulating a methylation status of one or more cytosine bases in the adult cell, wherein the regulating comprises contacting the adult cell that is isolated and purified with an effective amount of;
(i) an enzyme or fragment thereof that converts (a) 5-methylcytosine to 5-hydroxymethylcytosine, (b) 5-methylcytosine to an acid beyond hydroxymethlyation, or (c) 5-methylcytosine to an aldehyde beyond hydroxymethlyation;
(ii) an inhibitor that decreases or prevents hydroxymethylation;
or (iii) a combination thereof, andwherein the regulating the methylation status thereby modifies the cellular fate of the adult cell that is isolated and purified. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22)
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Specification