SUMMARY TADs, CTCF loop domains, and A/B compartments have been identified as important structural and functional components of 3D chromatin organization, yet the relationship between these features is not well understood. Using high-resolution Hi-C and HiChIP we show that Drosophila chromatin is organized into domains we term compartmental domains that correspond precisely with A/B compartments at high resolution. We find that transcriptional state is a major predictor of Hi-C contact maps in several eukaryotes tested, including C. elegans and A. thaliana. Architectural proteins insulate compartmental domains by reducing interaction frequencies between neighboring regions in Drosophila, but CTCF loops do not play a distinct role in this organism. In mammals, compartmental domains exist alongside CTCF loop domains to form topological domains. The results suggest that compartmental domains are responsible for domain structure in all eukaryotes, with CTCF playing an important role in domain formation in mammals.

Highlights d Intra-gene interactions cause the formation of gene domains that establish A compartments d RNAPII and cohesin promote, but condensin inhibits, formation of gene domains d Pairing between homologs occurs at 6-kb buttons enriched in architectural proteins d Condensin II antagonizes homolog pairing, whereas RNAPII and cohesin have no effect

In addition to its roles in controlling infection and tissue repair, inflammation plays a critical role in diverse and distinct chronic diseases, such as cancer, metabolic syndrome, and neurodegenerative disorders, underscoring the harmful effect of an uncontrolled inflammatory response. Regardless of the nature of the stimulus, initiation of the inflammatory response is mediated by assembly of a multimolecular protein complex called the inflammasome, which is responsible for the production of inflammatory cytokines, such as interleukin-1β (IL-1β) and IL-18. The different stimuli and mechanisms that control inflammasome activation are fairly well understood, but the mechanisms underlying the control of undesired inflammasome activation and its inactivation remain largely unknown. Here, we review recent advances in our understanding of the molecular mechanisms that negatively regulate inflammasome activation to prevent unwanted activation in the resting state, as well as those involved in terminating the inflammatory response after a specific insult to maintain homeostasis.

Background Circadian gene expression is essential for organisms to adjust their physiology and anticipate daily changes in the environment. The molecular mechanisms controlling circadian gene transcription are still under investigation. In particular, how chromatin conformation at different genomic scales and regulatory elements impact rhythmic gene expression has been poorly characterized. Results Here we measure changes in the spatial chromatin conformation in mouse liver using genome-wide and promoter-capture Hi-C alongside daily oscillations in gene transcription. We find topologically associating domains harboring circadian genes that switch assignments between the transcriptionally active and inactive compartment at different hours of the day, while their boundaries stably maintain their structure over time. To study chromatin contacts of promoters at high resolution over time, we apply promoter capture Hi-C. We find circadian gene promoters displayed a maximal number of chromatin contacts at the time of their peak transcriptional output. Furthermore, circadian genes, as well as contacted and transcribed regulatory elements, reach maximal expression at the same timepoints. Anchor sites of circadian gene promoter loops are enriched in DNA binding sites for liver nuclear receptors and other transcription factors, some exclusively present in either rhythmic or stable contacts. Finally, by comparing the interaction profiles between core clock and output circadian genes, we show that core clock interactomes are more dynamic compared to output circadian genes. Conclusion Our results identify chromatin conformation dynamics at different scales that parallel oscillatory gene expression and characterize the repertoire of regulatory elements that control circadian gene transcription through rhythmic or stable chromatin configurations.