在差异化诱导的基因激活过程中协调PIC组装和染色质重塑
Evi Soutoglou1, Iannis Talianidis
1Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Post Office Box 1527, 711 10 Herakleion, Crete, Greece.
概括
染色体重塑,而不是预启动复合体组合,定义了基因激活. 基因组乙转移酶和Brahma同质的招募先于核细胞重塑和转录启动在α1抗素促进体.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 染色体动力学 染色体动力学
背景情况:
- 了解基因转录启动过程中的事件的精确顺序对于破译基因调节至关重要.
- 人类α1抗素 (AAT) 基因在肠细胞分化过程中的激活,为研究促进体动态提供了一个模型.
- 在启动转录过程中,预启动复合组合,基因组修饰和染色质重塑的作用仍然是积极研究的领域.
研究的目的:
- 在基因激活过程中研究人类AAT促进体中分子事件的时间序列.
- 确定染色体重塑在预启动复合体形成和转录启动的背景下所起的作用.
主要方法:
- 通过使用诸如染色体免疫沉 (ChIP) 等技术,分析转录因子对AAT促进体的有序招募.
- 监测预启动复合物的组装,包括酸化RNA聚合酶II (Pol II).
- 评估酸转移酶 (CBP,P/CAF) 的活性以及染色体重塑剂 (hBrm) 的招募.
主要成果:
- 一个完整的预启动复合物,包括酸化RNA Pol II,在转录激活之前组装在促进体上.
- 招募了基因组乙转移酶CBP和P/CAF,但基因组过乙化被推迟.
- 人类Brahma同类 (hBrm) 的招募是暂时的,随后是与转录启动一致的核细胞重塑.
结论:
- 在人类AAT促进体中,染色质重构是定义转录启动的关键步骤.
- 染色体重塑发生在核心转录机械 (Pol II) 组装后.
- 这表明了一个模型,在这个模型中,预启动复合体组装先行,并且染色质重塑促进了转录的最终启动.
相关概念视频
Crossing Over
Unlike mitosis, meiosis aims for genetic diversity in its creation of haploid gametes. Dividing germ cells first begin this process in prophase I, where each chromosome—replicated in S phase—is now composed of two sister chromatids (identical copies) joined centrally.
The homologous pairs of sister chromosomes—one from the maternal and one from the paternal genome—then begin to align alongside each other lengthwise, matching corresponding DNA positions in a process called synapsis.
In order to...
The homologous pairs of sister chromosomes—one from the maternal and one from the paternal genome—then begin to align alongside each other lengthwise, matching corresponding DNA positions in a process called synapsis.
In order to...
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.
Gene 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...
Conservative 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...
Combinatorial Gene Control
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...
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...
Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...


