Inversion of the mouse α-globin super-enhancer reverses expression and interaction profiles of flanking genes. Contrary to the orientation-independent paradigm of enhancers, this super-enhancer acts in an orientation-dependent manner.

CDX2 binds distinct targets in developing and adult intestinal epithelial cells based on the distribution of its motifs with and without CpG. Here, the authors show that loss of DNA methylation during development allows Cdx2 to activate target genes.

Riboswitches are RNA sensors that allow bacteria to sense and respond to their environment. Here, Bushhouse et al. demonstrate that the sensitivity of several riboswitches can be tuned by manipulating how the riboswitch RNAs fold during transcription.

Here the authors reveal that in addition to promoting class switch recombination via inhibition of DNA end processing, RIF1 fine-tunes the kinetics of plasma cell differentiation, thus providing an additional layer of control in the establishment of humoral immunity.

Transcription elongation is an essential step for gene expression control but remains unclear during spermatogenesis. Here, the authors report that NKAPL, a testis-specific protein distantly related to RNA splicing factors, is a crucial regulator of transcription pause-release.

Duttke et al. show that transcription factors have position-dependent effects relative to their distance from the transcription start site, which suggests that a 'spatial grammar' could be used to encode multiple gene-regulatory programmes.

Transcription factors (TFs) and cis-regulatory elements (CREs) drive organism development. Suboptimal binding of TFs to CREs is shown to be key for the specificity of gene expression. New work now indicates that a similar principle governs the activities of TFs and their regulatory specificity.

A study describes the role of the ACTN2 enhancer in myocardial maturation, highlighting its relevance in regulating structural, functional and metabolic dynamics in the heart. These findings offer insights that may advance our understanding of cardiovascular disease.

To advance the toolset for controlling plant gene expression, we developed a CRISPR interference-based platform for the construction of synthetic Boolean logic gates that is functional in multiple plant species. These genetic circuits are programmable and reversible in nature, which will enable spatiotemporal control of plant responses to dynamic cues.

In this issue of Nature Metabolism, the research team of Mitchell Lazar reveals unexpected consequences of double loss of the coregulators NCOR1 and NCOR2 (NCOR1/2) in hepatocytes of adult mice, which affects chromatin functioning and glucocorticoid receptor (GR)-mediated gene transcription.

Carl G. de Boer highlights a recent paper by Lim et al. on the importance low-affinity transcription factor-binding sites for determining organismal phenotypes.