発達中の人間の遠脳に関するクロマチンのアクセシビリティ・アトラス

Eirene Markenscoff-Papadimitriou¹, Sean Whalen², Pawel Przytycki²

¹Department of Psychiatry, Langley Porter Psychiatric Institute, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.

Cell

|July 2, 2020

まとめ

科学者たちは発達中の人間の脳内のクロマチンをマッピングし遺伝子発現を制御する規制要素を見つけましたこのアトラスは神経発達や自閉症のような疾患における鍵となる強化因子とその役割を示しています

科学分野:

ゲノミクス
神経科学
発達生物学

背景:

遺伝子発現の特異性は人間の脳の発達に不可欠です
この特異性を駆動する規制要素を理解することは神経発達過程の解読の鍵です

研究の目的:

発達中の人間の脳にオープンクロマチンのアトラスを作るのです
脳の発達強化剤として機能する予測された調節要素 (pRE) を特定し,特徴づけること.
これらの要素が地域的,時間的,およびラミナルの遺伝子発現特異性における役割を調査する.

主な方法:

脳の領域と前頭皮質の層からオープンクロマチンのアトラスを生成した
開かれたクロマチン領域内の予測された規制要素 (pRE) を特定した.
遺伝子発現データと相関するクロマチンのアクセシビリティ
CRISPRの活性化 (CRISPRa) とマウスの変異遺伝子の実験を用いて,強化剤の機能を検証した.

主要な成果:

アクセシビリティの時間的,地域的,ラミナルの違いを示す pREを特定した.
PREのアクセシビリティと遺伝子発現の違いの相関関係が見つかりました
自閉症リスク遺伝子SLC6A1を調節するpREの機能的なde novo変異を発見した.
FEZF2とBCL11A遺伝子の近くのpREの強化活性が検証されました.

結論:

作成されたアトラスは,神経発達の遺伝子調節を理解するための貴重なリソースです.
pREは,発達中の脳における細胞型および領域特異的な遺伝子発現に重要な役割を果たします.
この研究は神経発達障害の遺伝的根拠についての洞察を提供します

キーワード:

ATAC-seq 自閉症クロマチン強化剤遺伝子調節機械学習神経発達神経精神疾患

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