UC Irvine

Gene expression at the transcriptional level is controlled by DNA sequences called cis-regulatory modules (CRM) and at the post-transcriptional level by microRNAs (miRNAs). CRMs have been studied almost exclusively in bilaterian organisms and little is known about them in non-bilaterian metazoans. Understanding the architecture of CRMs in cnidarians, a sister phylum to bilaterians, can potentially shed light on the evolution of gene regulation. Head regeneration is one of the most widely studied developmental processes in cnidarians. Using a comparison of the transcriptomes of regenerating heads and developing buds, I have determined sets of genes that are specific and common between head regeneration and budding. To understand the genomic sequences controlling these developmental programs, I have mapped the open-chromatin landscape of Hydra in different body parts and during head regeneration to identify candidate promoters and enhancers. My results are the first atlas of CRMs in Hydra, including a substantial fraction that is dynamic during head regeneration.

Mammalian embryonic development has been used as a model system to study the role of miRNAs in previous studies, but a complete atlas of miRNA expression during development is missing. To understand the role of microRNAs during mouse development, I analyzed a time course of development representing multiple tissues and organs in mouse embryo. We find distinct tissue and developmental stage-specific miRNA expression profiles dominated by a small number of miRNAs. Analysis of conserved miRNAs reveals clustering of expression patterns by tissue types rather than species. We used matching RNA-seq and histone modification ChIP-seq datasets to improve the annotation of miRNA primary transcripts. We show that the expression levels of majority of primary miRNA transcripts predict the expression of their corresponding mature miRNAs. Our data provide the most comprehensive miRNA resource for mouse as well as a comprehensive list of mouse miRNAs that can be reliably measured by RNA-seq of their primary transcripts.

Taken together, the elucidation of cis-regulatory landscape in the cnidarian Hydra and miRNA expression during mouse embryonic development will help the scientific community to understand better the role of enhancers in metazoan evolution and miRNA regulation in mammalian embryonic development.