Title:
Chromatin modification: from structure and function

 

Speaker:
Kiyoe Ura
Chiba University Graduate school of Science

 

Abstract:
The basic subunit of chromatin, the nucleosome, consists of DNA wrapped around an octamer of four core histones: H2A, H2B, H3 and H4, and linker histone H1. Chromatin modification, such as histone modifications and DNA methylation, are catalyzed and recognized by specific proteins, establishing unique modification patterns that act as chromatin signals. To understand the mechanism of regulation of chromatin modification, as well as their function in development, we have been studying on the structural and functional transition of chromatin both in the reconstituted chromatin and in the nucleus.
More recently, we demonstrated that a H3K36 methyltransferase NSD2, also known as WHSC1 or MMSET, functions for transcriptional regulation and that the NSD2 deficiency is responsible for Wolf-Hirschhorn syndrome (WHS). NSD2 is required for normal hematopoietic differentiation, especially for B cell development. Here, we show that mouse Nsd2 is involved in V(D)J recombination during B-cell development, suggesting the functional link between Nsd2 and DNA repair.
Transcription-associated DNA repair mediated by histone H3K36 methylation will be discussed.

 

References:
1.Saeki H., Ohsumi K, Aihara H, Ito T, Hirose S, *Ura K. and Kaneda Y. Linker histone variants control chromatin dynamics during early embryogenesis. PNAS. 102, 5697-5702, 2005
2.Nimura K., * Ura K., Shiratori H. Schwartz R. Ikawa M. Okabe M. and *Kaneda Y. A histone H3 lysine 36 trimethyltransferase linkes Nkx2-5 to Wolf-Hirschhorn syndrome. Nature, 460, 287-291, 2009
3.Kashiwagi K., Nimura K., *Ura K. and *Kaneda Y. DNA methyltransferase 3b preferentially associates with condensed chromatin. Nucleic Acids Res., 39, 874-888, 2011
4.Campos-Sanchez E. Deleyto-Seldas N, Dominguez V, Carrillo-de-Santa-Pau E, Ura K, 他11名, Cobaleda C*. Wolf-Hirschhorn Syndrome Candidate 1 Is Necessary for Correct Hematopoietic and B Cell Development., Cell Rep. 19, 1586-1601, 2017