ドロソフィラのゲノムのシス調節マップ
Nicolas Nègre1, Christopher D Brown, Lijia Ma
1Institute for Genomics and Systems Biology, Department of Human Genetics, The University of Chicago, 900 East 57th Street, Chicago, Illinois 60637, USA.
Nature
|March 25, 2011
まとめ
modENCODEプロジェクトは,広範囲にわたるクロマチンのデータを用いて,ドロソフィラ・メラノガスターの調節性ゲノムをマッピングしました. これは,20,000以上の候補規制要素を特定し,新しい転写因子相互作用を明らかにしました.
科学分野:
- ゲノミクスゲノミクスとは
- 分子生物学は分子生物学である.
- 発達生物学 発達生物学について
背景:
- 遺伝子調節要素の体系的な注釈は,ゲノム科学において極めて重要ですが,挑戦的です.
- 以前のドロソフィラの研究では,ポリコンブ反応要素や転写因子結合部位などの特定の規制要素を特定しました.
- 規制ゲノム全体の包括的なアノテーションは,未解決の課題です.
研究 の 目的:
- ドロソフィラ・メラノガスターの規制ゲノムに関する包括的な地図を作成する.
- プロモーター,エンハンスター,インソレータを含む候補規制要素を特定し,検証する.
- 転写因子結合関係を明らかにし,規制ネットワークを構築する.
主な方法:
- 染色体の8つの特徴,5つのヒストン脱酸化酵素と38の転写因子に関する300以上のChIP-seqデータセットを利用した.
- 統合されたデータセットから候補のCIS規制要素を推論するために,応用計算分析を行いました.
- 予測されるプロモーター,エンハンスター,および隔離剤のサブセットについて,in vivo検証を行いました.
主要な成果:
- ドロソフィラの調節性ゲノムの地図を作成し,20,000以上の候補の調節性要素を特定しました.
- プロモーター,エンハンスター,およびインソレータに関する検証された予測 in vivo.
- クロマチンの活性とアクセシビリティに関連した密度の高い転写因子結合のほぼ2,000の領域を特定しました.
- 何百もの新しい転写因子共同結合関係を発見し,800以上の潜在的な規制相互作用を持つネットワークを定義しました.
結論:
- modENCODEプロジェクトは,ドロソフィラのゲノム調節を理解するための貴重なリソースを提供します.
- この研究は,シス調節要素と転写因子ネットワークの包括的な注釈を大幅に前進させています.
- 発見は,開発中の規制要素と転写因子の複雑な相互作用についての洞察を提供します.
関連する概念動画
Position-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.
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...
Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
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...
Heterochromatin
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...
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...


