KOSEN 한인과학기술자네트워크

In eukaryotic cells, DNA is hierarchically packaged into higher order structures called chromatin. The basic unit of the chromatin is the nucleosome, which is formed from 146 base pairs of DNA wrapped around a histone octamer. Chromatin is a dynamic structure and can be modified in several ways through DNA methylation, covalent histone modification, ATP-dependent chromatin remodeling, and non-coding RNAs. The chromatin modifications can lead to inheritable trait changes without changing DNA sequence, known as ‘epigenetic memory’. The epigenetic memory is essential for stem cell pluripotency maintenance and embryonic development as well as in later stages of development. The perturbation of epigenetic memory can cause developmental defects, onset of cancers and may cause neurological disorders. However, molecular mechanisms of epigenetic gene regulation are largely unknown.

            Many proteins are involved in modifying chromatin and they function mostly as complexes.  Each component in the complex contributes to the function and activity of the complex. The defects in chromatin modifying complexes can lead to the diseases mentioned above. Unfortunately, little is known about the mechanisms of how the chromatin modifying complexes function as complexes, what the functional roles of each component in the complexes are, and how the complexes recognize the central unit of chromatin- the nucleosome.

            Elucidating three dimensional structures of the chromatin modifying complexes and each component in atomic details is likely to provide insights into the mechanisms of how the chromatin modifying complexes function. Furthermore, biophysical and biochemical approaches toward investigating interactions between the nucleosome and the epigenetic regulators will provide fruitful information on how epigenetic regulators recognize chromatin. Structural and biochemical studies on epigenetic regulators may illuminate molecular basis of epigenetic diseases and provide platforms for developing methods to cure the diseases.