Abstract:
Methods for reactivating genes on the inactive X chromosome that include administering one or both of a DNA methyltransferase (DNMT) Inhibitor and/or a topoisomerase inhibitor, e.g., etoposide and/or 5′-azacytidine (aza), optionally in combination with an inhibitor of XIST RNA and/or an Xist-interacting protein, e.g., a chromatin-modifying protein, e.g., a small molecule or an inhibitory nucleic acid (such as a small inhibitory RNA (siRNAs) or antisense oligonucleotide (ASO)) that targets XIST RNA and/or a gene encoding an Xist-interacting protein, e.g., a chromatin-modifying protein.
Abstract:
A DNA methyltransferase is derived from Deinococcus radiodurans and has a typical conservative structural domain of DNA methyltransferase. The DNA methyltransferase includes: an AdoMet binding region containing a “FxGxG” conservative sequence, a target sequence recognition region and a catalytic region containing a “TSPPY” conservative sequence sequentially from N-terminal to C-terminal; and belongs to α-type DNA methyltransferase category. The recognized substrate DNA conservative sequence is 5′-CCGCGG-3′, a methylation modified position is N4 site of second cytosine to generate a 4mC type modified base, and an optimum temperature for methylated reaction is in a range of 25-37° C. The DNA methyltransferase can specific-recognize the conservative motif of “CCGCGG” and methylate the N4 site of the second cytosine to produce the 4mC modified base, which is a N4-Cytosine DNA methyltransferase.
Abstract:
The present invention relates to the discovery of a novel restriction/modification system in Caldicellulosiruptor bescii. The discovered restriction enzyme is a HaeIII-like restriction enzyme that possesses a thermophilic activity profile. The restriction/modification system also includes a methyltransferase, M.CbeI, that methylates at least one cytosine residue in the CbeI recognition sequence to m4C. Thus, the invention provides, in various aspects, isolated CbeI or M.CbeI polypeptides, or biologically active fragments thereof; isolated polynucleotides that encode the CbeI or M.CbeI polypeptides or biologically active fragments thereof, including expression vectors that include such polynucleotide sequences; methods of digesting DNA using a CbeI polypeptide; methods of treating a DNA molecule using a M.CbeI polypeptide; and methods of transforming a Caldicellulosiruptor cell.