免疫特異的なAP-1-IRF複合体の組立と機能を指示するゲノム制御要素

Elke Glasmacher¹, Smita Agrawal, Abraham B Chang

¹Department of Discovery Immunology, Genentech, Incorporated, South San Francisco, CA 94080, USA.

Science (New York, N.Y.)

|September 18, 2012

まとめ

インターフェロン調節因子4 (IRF4) とBATFは,調節要素に協力して結合し,Tヘルパー17細胞の分化を促進します. このメカニズムは,様々な免疫細胞の免疫信号を統合します.

科学分野:

免疫学免疫学とは
分子生物学は分子生物学である.
遺伝学遺伝学とは

背景:

IRF4やIRF8のようなインターフェロン調節因子 (IRF) は,免疫細胞の分化に不可欠です.
IRFは通常,シス調節要素をEts因子と結合させるが,特定のEtsパートナーを持たないT細胞への標的化は不明である.

研究の目的:

IRF4がT細胞の遺伝子,特にTヘルパー17 (T(H) (17) 細胞を標的とするメカニズムを解明する.
T(H) 17細胞におけるIRF4媒介遺伝子調節に関与するDNAモチーフとタンパク質パートナーを特定する.

主な方法:

染色体免疫プレシピテーションシーケンシング (ChIP-seq) は,T(H) 17細胞で実施されました.
分析は,IRF4および他の転写因子によって共同結合されたDNA配列を特定することに焦点を当てました.

主要な成果:

IRF4は,T(H) 17細胞の活性化タンパク質1 (AP-1) - IRF複合元素 (AICE) を標的としたことが判明しました.
AP-1ファミリーのメンバーであるBATFは,AICEsでIRF4の重要な共同拘束パートナーとして特定されました.
IRF4とBATFは協力して様々なAICEと結合し,遺伝子活性化とT(H) 17の分化を促進します.

結論:

AICEモチーフは,IRF4とBATFの結合のための重要なゲノム制御要素として機能します.
AICEにおけるこのIRF4-BATF相互作用は,T(H) 17細胞の分化に不可欠であり,他の免疫細胞タイプでも利用されます.
発見は,特定の転写因子-DNA要素相互作用を通じて免疫調節信号を統合するための保存されたメカニズムを示しています.

さらに関連する動画

11:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

10:16

Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions

Published on: June 28, 2018

関連する概念動画

02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...

02:23

Master Transcription Regulators

02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...

02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...

02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...