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Nature Papers Examine How Topologically Associating Domains Form, Develop Atlas of MicroRNA Expression

Interphase chromosomes of animals are organized into compartments of active or repressive chromatin called topologically associating domains (TADs), but how these are formed is not entirely clear. To investigate, a team of scientists from the Southern University of Science and Technology in China assemble a high-quality reference genome of the frog Xenopus tropicalis, then perform high-throughput chromosome conformation capture analysis across multiple development stages on wild-type X. tropicalis embryos, as well as on X. tropicalis embryos in which certain genes associated with TAD formation in other organisms are silenced. As reported in Nature Genetics, they find that TAD establishment in X. tropicalis is similar to that in mice and flies, does not depend on zygotic genome transcriptional activation, and is followed by the sequential establishment of loop and stripe structures in later developmental stages. They also show that TAD formation requires the architectural proteins CTCF and Rad21, and that the chromatin remodeling factor ISWI is required for both TAD establishment and embryo development. The study's results "provide a rich resource for studying genome folding principles and the role of the 3D chromatin architecture in gene expression regulation, which governs cell differentiation and decides cell fate," the authors write.

An atlas of microRNA expression and regulatory element activity of the mouse immune system is published in this week's Nature Immunology. MiRNAs are required for proper immune cell development and function, but efforts to identify the miRNA profiles of different immune cells have been limited. At the same time, the promoter and enhancer landscape that controls the expression states of immune-linked miRNAs is poorly characterized. Aiming to build a resource that can support further study in this area, a group led by scientists from Mount Sinai and the Immunological Genome Consortium generate an miRNA expression atlas from 63 primary mouse immune cell populations spanning hematopoietic and stromal lineages. They then connect these profiles with ATAC-seq, ChIP-seq, and nascent RNA profiles to establish a map of miRNA promoter and enhancer usage in immune cells. The researchers find that miRNA complexity was relatively low, but that each cell type had a unique miRNA signature. Integration of miRNA expression with chromatin accessibility revealed putative regulatory elements for differentially expressed miRNAs. An integrated analysis of miRNA expression with chromatin accessibility across immune cells reveals putative regulatory elements for differentially expressed miRNAs and provides evidence of dominant or additive effects of different promoters for the same miRNA. "The use of multiple promoters supports a means to reach the high abundance required for miRNAs to achieve suppressive activity," the study's authors write.

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