核個体におけるOCT4-SOX2モチーフ読み取りのメカニズム

Alicia K Michael¹, Ralph S Grand¹, Luke Isbel¹

¹Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.

Science (New York, N.Y.)

|April 25, 2020

まとめ

転写因子 (OCT4とSOX2) は,その構造を変えることで,核細胞内でDNAを結合する. クロマチンの遺伝子調節要素にアクセスする方法を示しています

科学分野:

分子生物学
エピジェネティクス
構造生物学

背景:

転写因子 (TF) は,DNAを結合することによって遺伝子発現を制御する.
染色体の基本単位である核細胞はDNAを包み込み TFへのアクセスを制限します
遺伝子調節を解読するには,TF-核分裂体の相互作用を理解することが重要です.

研究の目的:

再プログラミング因子であるOCT4とSOX2が核細胞に占拠されたDNAモチーフに結合する方法を調査する.
塩基対解像度で核細胞DNAとの関わりの構造的基礎を決定する.

主な方法:

核染色体DNAにおけるTFのインビトロ測定
TF核細胞複合体の構造を決定するための冷凍電子顕微鏡
DNA歪みとヒストンの相互作用の分析

主要な成果:

OCT4とSOX2は,好ましい位置で核細胞DNAに結合し,差異的なDNA歪みを誘発する.
モチーフの方向性によって,TFはヒストンからDNAを異動させたり,局所的な歪みを引き起こしたりします.
OCT4はDNA結合ドメインを1つ利用して,核細胞内の部分的モチーフを認識します.

結論:

OCT4とSOX2は,サイト特異な結合を核細胞に示し,クロマチンの調節におけるその役割を説明する.
TFは結合されたDNAモチーフにアクセスするために核細胞構造を積極的に歪めることができます.
これらの発見は,TFが染色体DNAに結合するメカニズムの洞察を提供します.

さらに関連する動画

06:32

Deciphering Molecular Mechanism of Histone Assembly by DNA Curtain Technique

Published on: March 9, 2022

2.1K

08:01

Oct4GiP Reporter Assay to Study Genes that Regulate Mouse Embryonic Stem Cell Maintenance and Self-renewal

Published on: May 30, 2012

10.8K

関連する概念動画

02:32

Histone Modification

15.7K

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...

Histone Modification

Nucleosome Remodeling

10.6K

Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...

10.6K

02:25

Spreading of Chromatin Modifications

9.2K

The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...

9.2K

02:33

Combinatorial Gene Control

9.4K

Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...

9.4K

01:12

The Nucleosome Core Particle

2.0K

Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...