リシン修正酵素間のクロストークは,サイト固有のDNA増幅を制御する

Sweta Mishra¹, Capucine Van Rechem¹, Sangita Pal¹

¹Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, 13(th) Street, Charlestown, MA 02129, USA.

Cell

|July 31, 2018

まとめ

染色体調節体は腫瘍におけるDNA複製数の増加を制御する. 特定のH3K4メチル化経路と,KDM4BとKDM5Bを含む明確なネットワークは,サイト固有のDNA増幅を調節する.

科学分野:

エピジェネティクス
癌生物学
ゲノミクス

背景:

染色体DNA増幅は多くの癌の特徴です
KDM4Aが一時的なサイト固有の複製数 (TSSG) を獲得する役割は知られているが,これらの獲得を誘発する他のメカニズムは不明である.

研究の目的:

サイト固有のDNA複製の増殖を制御する新たなクロマチン調節物質を特定する.
H3K4メチル化状態と関連するレギュレータがTSSGをオーケストラするメカニズムを解明する.

主な方法:

H3K9/H3K36の調節剤と併用して,H3K4-調節するクロマチンの機能を調査した.
KDM5A,COMPASS/KMT2メチルトランスファーゼ,およびMLL1-KDM4B-KDM5BネットワークがDNA複製数を調節する役割を分析した.

主要な成果:

H3K4-修正クロマチンレギュレータが,TSSGをオーケストラするためにH3K9/H3K36レギュレータと協力することを発見した.
KDM5AとCOMPASS/KMT2メチルトランスフェラーゼは,H3K4メチル化とKDM4Aの徴集を通じてTSSGロキーを影響することを実証した.
KDM4A独立した経路 (MLL1-KDM4B-KDM5B) が特定された.

結論:

これらの発見は,サイト固有のDNA再複製と増幅を制御する表遺伝的アドレッシングシステムを明らかにしています.
この研究は,腫瘍に関連したDNA複製数の変化を誘導するクロマチンの複合的な相互作用を強調しています.

キーワード:

H3K36 について H3K4 について H3K9 について JmjC について K36M について KDMについて KDM4 について KDM5 について KMT MLL について SETD1B について TSSG について増幅するクロマチンエピジェネティクスヒストン再複製する

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