A joint research group of Waseda University, Okinawa Institute of Science and Technology Graduate University, and National Institute for Basic Biology has revealed for the first time in the world the basic structure of "heterochromatin," which is an inactivated chromosomal region.
Genomic DNA, which is the genetic information of eukaryotes, forms a complex (nucleosome) with a protein called histone, is folded compactly, and is stored in the cell nucleus.Since it is necessary to selectively read only the genes required in each cell during cell differentiation and tissue formation, the reading of genomic DNA is turned on (activated) due to the difference in the folding method. ) And off (inactivation) regions are said to be formed.
Among them, the region where the gene is constantly turned off in the human chromosome is called "heterochromatin", and it is considered to cause some kinds of cancers and infectious diseases.So far, heterochromatin has been known to have a structure containing a protein called HP1 and a histone trimethylation modification (H3K9me3), but it has not been clarified what kind of structure it actually is.
今回、本研究グループは、2つのヌクレオソームが連結された「ダイヌクレオソーム」とヒトのHP1との複合体を、H3K9me3を模倣したヒストンを用いて試験管内で再構成する手法を独自開発。この技術と最新のクライオ電子顕微鏡解析手法を組み合わせることによって、HP1が2つのヌクレオソームを架橋する形でH3K9me3を含んだヌクレオソームに結合するという、ヘテロクロマチンの立体構造基盤を明らかにした。
This discovery is thought to be an important stepping stone to elucidate the gene-off mechanism in heterochromatin, and is also an important step in elucidating the causes of carcinogenesis and infectious diseases due to deficiency of chromosome inactivation.
Paper information:[Molecular Cell] Structural Basis of Heterochromatin Formation by Human HP1
