5/15/2023 0 Comments Beige scid miceTargeting of the dCas9-Tet1 or -Dnmt3a fusion protein to methylated or unmethylated promoter sequences caused activation or silencing, respectively, of an endogenous reporter. It is demonstrated that fusion of Tet1 or Dnmt3a with a catalytically inactive Cas9 (dCas9) enables targeted DNA methylation editing. However, investigation of the functions of specific methylation events remains challenging. Mammalian DNA methylation is a epigenetic mechanism orchestrating gene expression networks in many biological processes. However, investigation of the functional significance of these DMRs remains a challenge due to lack of appropriate molecular tools that enable efficient editing of DNA methylation in a targeted manner. Importantly, these maps have allowed for the identification of differentially methylated regions (DMRs) at base pair resolution during different stages of normal development (Lister et al., 2013) as well as disease (De Jager et al., 2014 Doi et al., 2009 Landau et al., 2014). Owing to the advancement in sequencing technologies, single-nucleotide resolution methylation maps for many types of human and mouse cells and tissues have been depicted (Lister et al., 2009 Schultz et al., 2015). Abnormal DNA methylation has been observed in cancer and neurological disorders (Laird and Jaenisch, 1996 Robertson, 2005). Genetic studies have revealed that DNA methylation is essential for mammalian development and adaptation to environmental signals (Jaenisch and Bird, 2003 Li et al., 1992 Smith and Meissner, 2013). Mammalian DNA methylation at 5-cytosine plays critical roles in many biological processes, including genomic imprinting, cell fate determination, chromatin architecture organization, maintenance of cell identity, and regulation of gene expression (Bird, 2002 Cedar and Bergman, 2012 Jaenisch and Bird, 2003 Smith and Meissner, 2013). 6, 2022, and is being submitted electronically via Patent Center. The xml file is 2,27,220 bytes, was created on Dec. xml file containing the Sequence Listing is WIBR-158-102.xml. xml format in lieu of a paper copy and is hereby incorporated by reference into the specification. The Sequence Listing associated with this application is provided in. The government has certain rights in the invention. HD045022 awarded by the National Institutes of Health. This invention was made with government support under Grant Nos. PCT/US2017/047674 was published under PCT Article 21(2) in English. 19, 2016, the contents of which are hereby incorporated by reference in their entirety. 18, 2017, which claims the benefit of U.S. 19, 2019, which is a national stage filing under 35 U.S.C.
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