5.5
人类的DNA几乎有两米长。然而,它被压缩在一个直径只有几微米的微小细胞核内。为了达到这种程度的紧缩,DNA被组织成几个连续的层次,使其可以适应这样一个微小的空间。DNA排列最紧密的形式是在显微镜下可以观察到一个染色体在一个分裂的细胞中。
在染色体中,DNA两次缠绕在一个叫做组蛋白蛋白质八聚体核的蛋白…
组蛋白是一类体积较小且带正电荷的蛋白质,能与带负电荷的DNA紧密结合,形成称为核小体的结构。
核小体核心颗粒包含一个组蛋白八聚体,该八聚体由组蛋白H2A、H2B、H3和H4各两个分子组成。该核心颗粒被一段145至147个碱基对的DNA几乎缠绕两圈。
每种组蛋白都有一个短小且带正电荷的尾部,长度为11至27个氨基酸,有助于维持带负电荷的DNA缠绕在组蛋白周围。此外,相邻核小体核心颗粒的尾部之间可相互作用,促进DNA的包装。
核心颗粒旁边,一段长度可变的连接DNA像串珠一样将各个核心颗粒分隔开来。另一种组蛋白H1则起到夹子的作用,固定连接DNA的位置。
核小体共同作用,将长链 DNA 分子压缩成长度为其原始长度三分之一的染色质纤维。
View the full transcript and gain access to JoVE Core videos
Q1: What is a nucleosome and why is it important for DNA storage?
A nucleosome is a DNA-histone protein complex that represents the fundamental unit of DNA compaction. It consists of a histone octamer core—eight histone proteins—wrapped by 145 to 147 base pairs of DNA. Nucleosomes compress the nearly two-meter-long human DNA molecule into a chromatin thread one-third of its original length, enabling it to fit inside the nucleus.
Q2: How do histones interact with DNA in the nucleosome?
Histones are small, positively charged proteins that tightly associate with negatively charged DNA. Each histone has a positively charged tail 11 to 27 amino acids long that aids in keeping DNA wound around the histone core. These tails also interact with neighboring core particles, facilitating DNA packaging and maintaining the structural integrity of the nucleosome.
Q3: What role does histone H1 play in nucleosome structure?
Histone H1 acts as a clamp that keeps linker DNA in place. Linker DNA is a variable-length stretch of DNA that separates each nucleosome core particle, resembling beads on a string. By securing this linker DNA, H1 stabilizes the overall chromatin structure and contributes to higher-order DNA compaction.
Q4: Why are histone proteins highly conserved across species?
Histone proteins are highly conserved because they perform essential DNA compaction functions critical to cell survival. The amino acid sequences of core histone proteins remain remarkably similar even between distantly related species. For example, histone H3 differs by only four amino acids between a calf thymus and a pea plant, reflecting the fundamental importance of these proteins.
Q5: What is the composition of the histone octamer core?
The histone octamer core consists of eight histone proteins: two molecules each of histones H2A, H2B, H3, and H4. This protein complex forms the structural foundation of the nucleosome, around which 145 to 147 base pairs of DNA wrap nearly two complete turns. The octamer's positive charge attracts and binds the negatively charged DNA backbone.
Q6: How do non-histone proteins contribute to nucleosome function?
Non-histone proteins bind to the nucleosome complex and help maintain DNA compaction while organizing long chromatin loops. These proteins also regulate critical cellular processes including DNA replication and RNA synthesis. Though comprising only a small proportion of the nucleosome complex, non-histone proteins are essential for coordinating gene expression and DNA replication.
Q7: How does the nucleosome enable DNA to fit inside the cell nucleus?
Human DNA measures nearly two meters long but must fit inside a nucleus only a few microns in diameter. The nucleosome compresses DNA into a chromatin thread one-third of its original length. Nucleosomes can further coil into higher-order compact structures, achieving the sequential levels of organization necessary to package DNA into chromosomes visible during cell division.