異なる要因が特定のゲノム領域におけるヒストン変異H3.3の局所化を制御しています
Aaron D Goldberg1, Laura A Banaszynski, Kyung-Min Noh
1Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Cell
|March 10, 2010
まとめ
ヒストンH3.3の変異の局所化は,Hiraの陪伴者だけでなく,異なる要因によって導かれます. この表遺伝的メカニズムは,細胞の分化中に変化し,遺伝子調節とテロメアの安定性に影響を与えます.
科学分野:
- エピジェネティクス エピジェネティクス
- 分子生物学は分子生物学である.
- ゲノミクスゲノミクスとは
背景:
- ヒストンの変種,特にH3.3は,表遺伝子記憶と細胞状態の維持において重要な役割を果たします.
- H3.3の堆積の正確なメカニズムを理解することは,遺伝子調節と分化を理解するために不可欠です.
研究 の 目的:
- 哺乳類の胚性幹細胞とニューロン前駆細胞における全ゲノムにわたるH3.3変異の分布をマッピングする.
- 様々なゲノム位置におけるH3.3の局所化における特定のシャペロンおよび関連するタンパク質の役割を明らかにする.
主な方法:
- 固有のH3.3.3.をタグするゲノム編集のための亜鉛指核酸を使用した.
- ゲノム全体のプロファイリング,免疫 afinity 浄化,および質量スペクトロメトリを実行しました.
主要な成果:
- H3.3の分布パターンは,配列に依存し,細胞分化中に動的に調節される.
- ヒラ・チャペロンは,H3.3の濃縮には,活性遺伝子や抑制遺伝子に欠かせないが,テロメアやすべての転写因子結合部位には欠かせない.
- AtrxとDaxxはHiraとは無関係にH3.3と結合し,AtrxはH3.3のテロメアの局所化とテロメアのRNA抑制に不可欠である.
結論:
- 多数の異なるタンパク質因子が,H3.3の局所化を特定のゲノム領域に媒介する.
- 細胞の分化には,H3.3変種分布のダイナミックな表遺伝的再プログラムが含まれています.
関連する概念動画
02:30Histone Variants at the Centromere
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3 variants are also...
02:32Histone Modification
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 deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:32Histone Modification
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 deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:32Position-effect Variegation
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
01:01Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...