Asymmetrical nucleosomal DNA signatures regulate transcriptional directionality

Nucleosomes are the basic units of chromatin. Despite their symmetrical structure, in vitro studies have shown that transcription across nucleosomes proceeds with different efficiency depending on the orientation of the 147 bp of DNA around the histone core. Here, we report that the proximal and distal halves of nucleosomal DNA contribute differentially to nucleosome stability in the genome context in vivo. In +1 nucleosomes (+1N), this asymmetry facilitates or prevents transcription depending on the orientation of its underlying DNA and is associated with an asymmetrical interaction between DNA and histones. These functional and structural proporties are encoded in the DNA signature of +1N since its incorporation into dowstream nucleosomes along the gene renders them asymmetrically accesible to MNase and inverts the balance between sense and antisense transcription depending on the orientation on the signature. Altogether, our results show that nucleosomal DNA endows nucleosomes with asymmetrical properties that modulate the directionality of transcription.