ヒストンH3ライシン27メチルトランスファーゼによるヘテロクロマティックDNA複製の調節
Yannick Jacob1, Hume Stroud, Chantal Leblanc
1Department of Biology, Indiana University, 915 East Third Street, Bloomington, Indiana 47405, USA.
Nature
|July 16, 2010
まとめ
アラビドプシスのヒストン修飾物質ARABIDOPSIS TRITHORAX-RELATED PROTEIN5 (ATXR5) とATXR6の変異により,アラビドプシスのDNAが再複製される. この研究は,ヘテロクロマチンの過剰複製を防止し,トランポゾン発現に影響を与える新しい経路を明らかにしています.
科学分野:
- 分子生物学は分子生物学である.
- エピジェネティクス エピジェネティクス
- 植物科学 植物科学について
背景:
- 細胞周期の調節により,細胞周期ごとに1回以上のDNA複製を防ぐ.
- ゲノム起源における複製前の複合体は,DNA複製を制御するための重要な標的である.
- ヒストンの改変は,遺伝子発現とゲノムの安定性を調節する上で重要な役割を果たします.
研究 の 目的:
- DNA再複製を防止するヒストン3ライシン27 (H3K27) モノメチルトランスファーゼATXR5およびATXR6の役割を調査する.
- ATXR5とATXR6.6の突然変異により再複製が起こりやすいゲノム領域を特定する.
- ATXR5とATXR6の変異がトランポゾン発現と植物発達に与える影響を理解する.
主な方法:
- 機能的なATXR5およびATXR6.6が欠けているアラビドプシスの変異体の遺伝子解析.
- DNA再複製の場所を特定するための全ゲノム分析.
- 特定のゲノム位置におけるH3K27単メチル化レベルの分析.
- トランポゾンにおける遺伝子発現分析.
- 植物発達のフェノタイプ分析.
主要な成果:
- ATXR5 と ATXR6 の突然変異は,アラビドプシスの特定のゲノム部位の再複製につながります.
- 再複製された領域は,主にトランポゾンや他の繰り返し,静かなゲノム要素に対応します.
- これらの再複製部位では,高レベルのH3K27単甲基化が観察されました.
- ATXR5/ATXR6の触媒SETドメインの変異は,再複製欠陥を引き起こすのに十分であった.
- ATXR5とATXR6の変異は,トランポゾン発現のアップレギュレーションと発達異常をもたらしました.
結論:
- ATXR5とATXR6は,アラビドプシスのヘテロクロマチンのDNA過剰複製を防ぐ新しい経路で機能します.
- ATXR5/ATXR6によるH3K27のモノメチル化は,重複する要素での再複製を抑制するために重要である.
- この経路の調節不良は,ゲノム安定性,トランポゾン活性,および植物発達の影響を及ぼします.
さらに関連する動画
関連する概念動画
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.
02:31Homologous Recombination
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
02:08Gene Conversion
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
02:53Conservative Site-specific Recombination and Phase Variation
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
02:46Genome Copying Errors
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
02:08Gene Conversion
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...