Divergent transcription and epigenetic directionality of human promoters

Genome-wide datasets measuring nascent RNA have revealed that active human promoters frequently display divergent transcription, generating a stable mRNA in the forward direction toward the gene and a typically unstable one in the reverse direction away from the gene. Recent work has shown that these transcripts originate from two distinct core promoters within a single nucleosome-free region (NFR). Different levels of forward and reverse activity lead to a wide range of directionality for promoter NFRs. Importantly, directionality is also reflected in the epigenetic modifications of nucleosomes immediately adjacent to the NFR. Here, we review the current literature pertaining to divergent transcription from promoter NFRs and its association with combinatorial histone post-translational modifications, or chromatin states, on upstream and downstream nucleosomes. Finally, we discuss several models to interpret the directionality of promoter chromatin states.