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Yun Chen, Albin Sandelin, Torben Heick Jensen and colleagues describe general rules governing the expression of reverse-oriented promoter upstream transcripts (PROMPTs) based on the orientation and proximity of promoter pairs. They characterize how the distance between promoters affects the expression of PROMPTs and the usage of alternate mRNA transcription start sites.

Maternal immune activation during pregnancy can negatively impact the developing fetus. Here, applying multi-omics (RNA-seq, phosphoproteomics and lipidomics) and imaging, the authors show that while maternal immune activation induces strong innate response in maternal organs it does not extend through the placenta but leads to fetal metabolic changes.

The improving functional annotation of genomes through the analysis of genome-wide data sets is revealing important characteristics of promoters. Similar classes of promoters are now emerging across diverse metazoan species, and novel features that contribute to gene regulation are being identified.

Most mammalian promoters are inherently bidirectional, but transcription only elongates productively in one direction. Data presented in this paper demonstrate that at least part of the answer lies in the asymmetric distribution of polyadenylation-site sequences around human gene promoters causing termination of upstream antisense transcription.

A study from the FANTOM consortium using single-molecule cDNA sequencing of transcription start sites and their usage in human and mouse primary cells, cell lines and tissues reveals insights into the specificity and diversity of transcription patterns across different mammalian cell types.

Piero Carninci and colleagues report the discovery of a large class of noncoding RNAs, non-annotated stem cell transcripts (NASTs), which are implicated in the regulation of stem cell properties. The authors identify 8,873 mouse and 3,042 human NASTs and functionally validate 4 as having an important role in the maintenance of pluripotency.

Activating transcriptional regulatory elements have traditionally been categorized into promoters, which define transcription start sites, and enhancers, which act distally to stimulate transcription. In this Review, Andersson and Sandelin discuss the latest findings from methodologies for profiling and testing transcriptional regulatory elements at scale. They explain how the data support an updated, nuanced model that accounts for the numerous overlapping molecular properties of promoters and enhancers.

Using the FANTOM5 CAGE expression atlas, the authors show that bidirectional capped RNAs are a signature feature of active enhancers and identify over 40,000 enhancer candidates from over 800 human cell and tissue samples across the whole human body.

Despite our growing understanding of their complexity, different types of RNA are still classified using technical rather than functional criteria. Andersson et al.show that categorization of RNAs based on stability and direction of transcription is an effective means of functional classification.

The small intestine forms via crosstalk between epithelial and mesenchymal cell compartments. Here, the authors show that a gradient of Wnt signalling along the anterior-posterior axis regulates Sonic Hedgehog which is required for correct formation and regionalization of the small intestine.

Many SNPs associated with inflammatory bowel disease are located in non-coding genomic regions. Here, the authors perform CAGE-sequencing on descending colon biopsies of Crohn’s disease and ulcerative colitis patients to map transcription start sites and enhancer activity for analysis of regulatory regions.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

Genome-wide discovery and characterization of core promoters has revealed that most mammalian genes are transcribed from multiple promoters, each of them starting from multiple nucleotide positions, not directed by a TATA box. The authors propose a new classification of promoters.

The nature of small RNA species derived from gene termini and intron-exon junctions is now further examined. By sequencing transcripts between 12 and 100 nucleotides derived from cells depleted for RNA decay factors as well as those associated with Argonaute proteins, insights into how these RNAs are produced is provided. Moreover, new small RNAs are identified.

The next step after sequencing a genome is to figure out how the cell actually uses it as an instruction manual. A large international consortium has examined 1% of the genome for what part is transcribed, where proteins are bound, what the chromatin structure looks like, and how the sequence compares to that of other organisms.

The FANTOM4 study identified transcriptional start sites active during proliferation arrest and differentiation of the human monocytic cell line THP-1. Systematic knockdown of 52 transcription factors provide support for their model in which a complex transcriptional network regulates the differentiation process.

An atlas of microRNA expression patterns and regulators is produced by deep sequencing of short RNAs in human and mouse cells.