Certain embodiments are directed to compositions and methods for solving problems associated with measuring T:G mispairs, U:G mispairs and other 5-substituted uracil mispairs. Certain embodiments are directed to a hybrid enzyme that is capable of finding and cutting the T of the T:G mispair or other mispaired uracil analogs creating a method for their measurement. In certain embodiments the hybrid enzyme is a fusion of a human thymine DNA glycosylase (TDG) activator segment and a catalytic domain of an archaeal thermophilic thymine glycosylase (tTDG).

Examples provided herein are related to detecting methylcytosine and its derivatives using S-adenosyl-L-methionine analogs (xSAMs). Compositions and methods for performing such detection are disclosed. A target polynucleotide may include cytosine (C) and methylcytosine (mC). The method may include (a) protecting the C in the target polynucleotide from deamination; and (b) after step (a), deaminating the mC in the target polynucleotide to form thymine (T). Protecting the C from deamination may include adding a protective group to the 5 position of the C, e.g., using a methyltransferase enzyme that adds the first protective group from an xSAM.

Provided herein are, inter alia, compositions and methods for demethylating and methylating a target DNA sequences in a mammalian cell. The compositions and methods are, inter alia, useful for modulating the expression of a target gene, or to create a gene regulatory network.

Provided herein are, inter alia, compositions and methods for the delivery of enhanced demethylation activity to target DNA sequences in a mammalian cell. The compositions and methods are, useful for activity modulation of a targeted gene, or to create a gene regulatory network.

Disclosed herein is a modified transposon end sequence comprising a mosaic end sequence, wherein the mosaic end sequence comprises one or more mutation as compared to a wild-type mosaic end sequence, wherein the mutation comprises a substitution with a uracil, an inosine, a ribose, an 8-oxoguanine, a thymine glycol, a modified purine, or a modified pyrimidine. Also disclosed are transposome complexes comprising these modified transposon end sequences and methods of library preparation using these modified transposon end sequences.

Compositions and methods are provided for treating and/or preventing lymphangiogenesis in a subject by using an inhibitor of a galectin-8 protein in an amount effective to inhibit or to modulate an activity of the galectin-8 protein or a portion thereof sufficient to inhibit the lymphangiogenesis associated with cancer, corneal injury, dry eye disease, inflammation, lymphedema, organ rejection or graft rejection.

The invention provides methods for enhancing the cytotoxicity of DNA damage in cancer cells that express thymine DNA glycosylase, and treating tumors accordingly. The methods comprise inhibiting the expression or biologic activity of thymine DNA glycosylase, and inducing DNA damage in the cancer cells. DNA damage may be induced by administration of bendamustine or gemcitabine to the cancer cells.

Compositions and methods are provided for treating and/or preventing lymphangiogenesis in a subject by using an inhibitor of a galectin-8 protein in an amount effective to inhibit or to modulate an activity of the galectin-8 protein or a portion thereof sufficient to inhibit the lymphangiogenesis associated with cancer, corneal injury, dry eye disease, inflammation, lymphedema, organ rejection or graft rejection.