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How expression of tissue-restricted self-antigens (TRA) is coordinated in medullary thymic epithelial cells (mTECs) remains unclear. Steinmetz and colleagues use single-cell RNA-sequencing to describe clusters of co-expressed TRAs.

Velten et al. use single-cell transcriptomics and functional data to map the early lineage commitment of human haematopoietic stem cells as a continuous process of cells passing through transitory states rather than demarcating discrete progenitors.

Antisense transcription is increasingly being recognized as an important regulator of gene expression across all kingdoms of life and through a range of regulatory modes. Antisense transcripts are also emerging as facilitators of rapid evolution of gene regulation.

Variation among RNA transcript isoforms can be generated from alternative start and polyadenylation sites, and results in RNAs and proteins with different properties being generated from the same genomic sequence; here a new method termed transcript isoform sequencing is described in yeast, and the method allows a fuller exploration of transcriptome diversity across the compact yeast genome.

One of two papers in this issue that reveal the prevalence of cryptic or hidden transcription in the yeast genome. Cryptic unstable transcripts (CUTs) are a major class of RNA polymerase II transcripts in budding yeast and are degraded immediately after being synthesized. In these papers, high-resolution genome analyses reveal that CUTs arise predominantly from promoter regions and in an antisense direction. There is therefore a widespread occurrence of inherently bidirectional promoters in yeast.

One of two papers in this issue that reveal the prevalence of cryptic or hidden transcription in the yeast genome. Cryptic unstable transcripts (CUTs) are a major class of RNA polymerase II transcripts in budding yeast and are degraded immediately after being synthesized. In these papers, high-resolution genome analyses reveal that CUTs arise predominantly from promoter regions and in an antisense direction. There is therefore a widespread occurrence of inherently bidirectional promoters in yeast.

H3K36 methylation by Set2 targets Rpd3S histone deacetylase to transcribed mRNA genes, repressing internal cryptic promoters and modulating elongation. Here, the authors provide evidence that the Set2-Rpd3S pathway also regulates dynamic expression of mRNAs and lncRNAs.

Human pluripotent stem cells were used to develop dorsal and ventral forebrain 3D spheroids, which can be assembled to study interneuron migration and to derive a functionally integrated forebrain system with cortical interneurons and glutamatergic neurons.

Effective treatment options for mitochondrial diseases are scarce. Here, Aiyar et al. identify the TIM23 mitochondrial protein sorting machinery as a potential intervention point for mitochondrial ATP synthase disorders.

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 method to introduce defined mutations into the yeast genome enables saturation mutagenesis of a gene and genome-scale introduction of genetic variants.

Microglia can expand and divide quickly in the context of CNS pathology, but little is known about the kinetics and clonality of microgliosis. Prinz and colleagues develop a new fate mapping system to monitor microglial dynamics. Microglial self-renewal is found to be a stochastic process under steady state conditions, whereas clonal expansion is observed during disease.

MSL1, a component of the Drosophila dosage compensation complex, genetically and biochemically interacts with CDK7, a subunit of the TFIIH transcription factor, thus revealing a complex interplay between MSL1 and the general transcriptional machinery.

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.

Variation in the regulation of gene transcription between individuals is thought to be a major cause of phenotypic diversity. Here, individual differences in the binding of transcription-factor proteins are studied. A well-known transcription factor in the yeast pheromone pathway is used as an example, and the underlying genetic loci responsible for variation in its binding are mapped. The study reveals new insights into the mechanisms of gene regulation, and new regulators of the yeast pheromone pathway.

The neuron-specific transcription factor Myt1l represses many somatic lineage programs, but not the neuronal lineage program, to both induce and maintain neuronal identity.

5PSeq is a method for studying ribosome dynamics based on co-translational mRNA decay. Genome-wide sequencing and quantification of 5′ phosphorylated mRNA degradation products allows the positions of the last translating ribosomes to be determined.

TIF-Seq uses paired-end sequencing of genome-wide circular cDNA libraries to determine the 5′ and 3′ ends of each full-length transcript; the design maximizes intramolecular ligation to ensure that each read originates from a single transcript.