Epigenome editors for modulating hiv transcription

Abstract

BrecOFF is an epigenome editor that specifically targets the HIV promoter, long tandem repeat (LTR), to deposit DNA and histone repressive markers and thereby silencing its transcription and reactivation. BrecOFF comprises of 3 modules (FIG. 1a). The DNMT3A and cofactor DNMT3L are the de novo DNA methylation machinery that marks DNA with repressive methylation marks. The Krüppel associated box (KRAB) domain is a transcriptional repression domain by recruit of TRIM28 repression complex and addition of repressive epigenetic marks on histones. Finally, dBrec1 is a catalytically inactive version of Brec1, a Cre-based directly evolved recombinase that specifically recognizes the R region of the HIV LTR without off-target effects

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