In eukaryotic cells, the genomic DNA interacts with proteins and folds into the basic structure termed chromatin, which in turn is further packaged with other proteins into layers of folded structure to form chromosome. Within the chromatin structure, proteins of various sorts bind to and fold tightly with the genomic DNA. Chromatin and its higher order structure chromosome constitute a sophisticated body to store and maintain DNA with the encoded genetic information, and at the same time to regulate the ON/OFF state of gene expression. We are investigating the process of chromatin and chromosome formation as well as the mechanism regulating the ON/OFF state of gene expression.

Efficient utilization of rapidly accumulating genomic information is extremely important for the advancement of biological as well as medical sciences. At the same time, it has a high impact on the development of a broad range of industries producing useful biological substances. Since the technologies we have developed to produce HAC (human artificial chromosome; see below) enable us to manipulate DNA and a number of proteins into a variety of chromatins, it is now possible to construct HAC’s capable of proper segregation and of regulation of expression of the integrated genes of useful functions. As mentioned above, we have developed technologies to construct HAC for the first time in the world by introducing natural DNA or artificially synthesized DNA into human tissue cultured cells: we observed that the HAC thus constructed was stably maintained throughout cell divisions. Our HAC technologies have already been used to introduce multiple genes simultaneously into a single cell, and HAC’s possessing artificially synthesized DNA are proven to be powerful tools to investigate the mechanisms of formation of chromatins and chromosomes as well as how they function in regulating the ON/OFF state of gene expression.

Needless to mention, our HAC technologies will become essential in the rapidly emerging field of synthetic genome research, including development of an ON/OFF switch for gene expression, production of useful materials through co-operative expression of multiple genes that are interrelated with each other for a synthetic metabolism, functional analysis of chromosome organization, and so on, in the foreseeable future.

Hiroshi Masumoto
Laboratory Head
Molecular biology, Cell biology, Chromosome segregation, Human artificial chromosomes, Synthetic biology

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• Hiroshi Masumoto masumoto [at] kazusa.or.jp
• Youichi Ogawa yogawa [at] kazusa.or.jp
• Koichiro Otake kotake [at] kazusa.or.jp
• Miyuki Inde
• Ayami Sakuma
• Yukiko Eifuku

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