A03-2 Genome modality of development and differentiation

The aim of our project is to elucidate the role of cohesin and its related factors in the development and differentiation. To date, we have shown that cohesin, one of the SMC protein complexes, has an essential role in chromatin conformation (chromatin loop formation). Loss-Of-Function mutations in cohesin-related genes, such as cohesin subunits and cohesin loaders, are responsible for Cornelia de Lange (CdLS) syndrome, which is characterized by disorder of development and differentiation. Gain-of-function mutations in the transcription elongation factor AFF4 and loss-of-function mutations in BRD4 are also responsible for CdLS-like diseases. These facts strongly suggest that cohesin is located in the transcriptional machinery. This study aims to clarify the role of cohesin-related factors in the development and differentiation by analyzing iPS cells derived from patients with CdLS-related diseases. By utilizing genomics, genetics and biochemistry we will try to understand the mechanisms behind the diseases. In parallel with these studies, various genome analysis technologies such as Pore-C, Hi-C, ChlA-Drop, scRNA-seq, quantitative ChIP-seq, eSPAN, micro-C, etc. will be introduced and open to other group members.

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