||Friday, 4 November 2011, 16:00～
||Seminar-shitsu 1,2, IDAC Research Bldg.
||Transcriptional regulation of Shh via chromosomal dynamics
||Mammalian Genetics Laboratory, National Institute of Genetics
||Yusuke WATANABEDevelopmental neurobiology (ex 8596)
||Recent studies indicate that accurate transcriptional regulation requires changes in higher-order chromatin structure. Expression of Shh, which encodes a signaling protein and plays pivotal roles for vertebrate morphogenesis, is regulated by several tissue specific enhancers. It provides an ideal model for understanding how transcriptional regulation is orchestrated by changes in the chromosomal structure. In the mouse limb bud, the posterior localized expression of Shh is regulated by a long-range enhancer, MFCS1, residing at about 1Mb upstream of the Shh promoter. Our previous study using 3D-FISH revealed a close proximity of MFCS1 to the Shh coding sequence, being associated with the transcriptional activity of Shh. However, molecular basis underlying this chromosomal dynamics has been unclear. To know how the long-range interaction occurs, we conducted chromosome conformation capture (3C) assays and generated transgenic mice with BAC DNAs as a model for studying the enhancer–promoter interaction. Involvement of some other genomic regions in transcriptional regulation by MFCS1 will be discussed.