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Keywords : chromatin, epigenetics, non-coding RNA, gene expression, genome rearrangement.
In eukaryotes, chromatin structure locally takes condensed and extended forms to regulate gene expression. This process called chromatin remodeling is closely related to histone modifications (i.e.acetylation, methylation etc.). Chromatin acquires modifications during cell differentiation and organism development, and the pattern of these alterations are passed on and maintained through cell division. In other words, differences in chromatin structure allow cells with identical genome sequences to develop a completely different pattern of gene expression. The study of such phenomenon is called Epigenetics.
Our main interest is how chromatin structure and epigenetic modifications interrelate with gene expression and genomic rearrangement including for example DNA recombination. On the one hand, recombination produces genetic diversity in germ cells and immune cells. On the other hand, it accounts for loss of genome integrity in cancer cells. It can be said that it is a double-edged sword. A lot remains unclear in this field of research, but it has become more and more popular in recent years. Moreover, this field is also extremely important for biotechnology. Based on fundamental research, our lab has developed methods such as the ADLib system for the generation of monoclonal antibody - for which we were awarded a prize from the Ministry of Education - and the TaqI system, a large-scale genome modification technique.
Concerning chromatin structure and gene expression, we are currently investigating how non-coding RNAs - RNAs which are not translated into protein - are related to histone modifications and chromatin structure. As the human genome was decoded, one of the biggest surprises was that only 1% of it is used as genes. All the rest having an unknown function, it was used to be called junk DNA. Nevertheless, we have started to understand that some of these regions are transcribed into countless non-coding RNAs, some of which are directly involved in the regulation of gene expression. In other words, what would be call the dark matter of genomics appears to play an important hidden role. Using genome-wide analysis technology such as next-generation high speed sequencers and genome tiling arrays, we are seeking to elucidate the function of these non-coding RNAs.
Professor Kunihiro Ohta
1. Genomic rearrangements and relationship to chromatin structure/epigenome.