B細胞特異のXIST複合体は,X不活性化を強制し,非典型のB細胞を抑制する
Bingfei Yu1, Yanyan Qi1, Rui Li1
1Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
Cell
|March 18, 2021
まとめ
TLR7のような免疫遺伝子を静止するために,長時間非コーディングRNAXISTは成人のB細胞に不可欠である. ループスやCOVID-19のような疾患における 制御不全は 性別の違いにおける 役割の拡大を強調しています
科学分野:
- 遺伝学
- 免疫学
- エピジェネティクス
背景:
- 長い非コーディングRNAのXISTは,初期の発達期にX染色体不活性化 (XCI) を開始する.
- XISTは,XCIが最初に確立された後,ほとんど必要ないと考えられていた.
研究 の 目的:
- 成人のヒトB細胞におけるXISTの継続的な役割を調査する.
- X-リンクされた免疫遺伝子の調節におけるXISTの機能とその病気への潜在的な関与を探求する.
主な方法:
- XIST RNA誘導プロテオミクスとCRISPR干渉 (CRISPRi) スクリーニング
- システミック・ルプス・エリテマトーサスとCOVID-19の患者からの単細胞トランスクリプトームデータの分析.
- DNAメチル化とヒストン脱酸化を含むXIST依存遺伝子調節を調査した.
主要な成果:
- TLR7を含む特定のX関連免疫遺伝子を静止するために,XISTは成人ヒトのB細胞に絶えず必要とされています.
- XIST依存遺伝子は,プロモーターDNAメチル化が欠けていて,継続的なヒストン脱酸化を必要とする.
- TRIM28はB細胞におけるXIST複合体の重要な構成要素として特定され,X結合遺伝子プロモーターのPol II中介である.
- XISTの異常とXIST依存性遺伝子の脱出は,狼またはCOVID-19の女性患者からのCD11c+非典型記憶B細胞 (ABCs) で観察されました.
- TLR7アゴニズムと組み合わせたXIST不活性化により,同型交換ABCが促進された.
結論:
- XISTは,異なる lncRNA- タンパク質複合体を通して,細胞型特異な機能を発揮する.
- XISTは,成人B細胞における免疫遺伝子の発現を調節する上で重要な役割を果たしています.
- XISTの調節障害は病気の発生に寄与し,性に基づく生物学的違いと医学におけるその重要性を強調しています.
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