Regulation of chromatin accessibility by small non-coding RNAs

MUNSTERBERG_U22DTP

Skeletal muscle is important for health and well-being throughout life. To understand better the factors that contribute to the maintenance of this important tissue, we study its development in the embryo. It is known that many of the genes and mechanisms that control embryo development are conserved across species and perform similar functions in adult organisms. This is also the case for small non-coding RNAs, called microRNAs, which are highly expressed in developing and mature skeletal muscles, where they can have protective function, for example in ageing or disease. To discover the full potential of microRNAs for healthy muscles we are using functional experiments in early avian embryos in ovo. We showed that muscle specific microRNAs, so-called myomirs, negatively regulate the expression of crucial transcription factors and epigenetic regulators (Pax3, Gli3, BAF60a/b). This is essential to provide robustness to developmental timing during the progenitor to myoblast transition, and to stably establish the myogenic differentiation programme. This new project will investigate further the role of myomirs for chromatin accessibility and thus the regulation of gene expression in embryo myogenesis. Using established experimental manipulations followed by genome-wide analysis using next generation sequencing, the student will characterize chromatin accessibility and identify novel cis-regulatory elements (CRE). These will be validated in vivo using time-lapse imaging and CRISPR-editing and their role in early muscle development will be tested. The student will be fully integrated into a lively laboratory investigating different aspects of skeletal muscle and cardiac development in avian embryos.

References

– Mok, G.F., et al., Characterising open chromatin in chick embryos identifies cis- regulatory elements important for paraxial mesoderm formation and axis extension. Nature Comms, 2021. DOI 10.1038/s41467-021-21426-7

– Mok, G.F., et al., miR-133-mediated regulation of the Hedgehog pathway orchestrates embryo myogenesis. Development, 2018. 145(12). DOI 10.1242/dev.159657

– Goljanek-Whysall, K., et al., myomiR-dependent switching of BAF60 variant incorporation into Brg1 chromatin remodeling complexes during embryo myogenesis. Development, 2014. 141(17). DOI 10.1242/dev.108787