Promoters of developmental genes in embryonic stem cells (ESCs) are marked by histone H3 lysine 4 trimethylation (H3K4me3) and H3K27me3 in an asymmetric nucleosomal conformation, with each sister histone H3 carrying only one of the two marks. These bivalent domains are thought to poise genes for timely activation upon differentiation. Here, we show that asymmetric bivalent nucleosomes recruit repressive H3K27me3 binders but fail to enrich activating H3K4me3 binders, thereby promoting a poised state.
View Article and Find Full Text PDFIn vitro transcription (IVT) is a technology of vital importance that facilitated the production of mRNA therapeutics and drove numerous breakthroughs in RNA biology. T7 polymerase-produced RNAs can begin with either 5'-triphosphate guanosine (5'-pppG) or 5'-triphosphate adenosine (5'-pppA), generating potential agonists for the RIG-I/type I interferon response. While it is established that IVT can yield highly immunogenic double-stranded RNA (dsRNA) via promoterless transcription, the specific contribution of initiating nucleosides to this process has not been previously reported.
View Article and Find Full Text PDFGenomes are organised into DNA loops by the Structural Maintenance of Chromosomes (SMC) proteins. SMCs establish functional chromosomal sub-domains for DNA repair, gene expression and chromosome segregation, but how SMC activity is specifically targeted is unclear. Here, we define the molecular mechanism targeting the condensin SMC complex to specific chromosomal regions in budding yeast.
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