Question

In July 2000, the Protein Data Bank named the nucleosome “molecule of the month.” In an accompanying report, David Goodsell wrote that

"The job of the nucleosome is paradoxical, requiring it to perform two oppo- site functions simultaneously. On one hand, nucleosomes must be stable, forming tight, sheltering structures that compact the DNA and keep it from harm. On the other hand, nucleosomes must be labile enough to allow the information in the DNA to be used. Polymerases must be allowed access to the DNA, both to transcribe messenger RNA for building new proteins and to replicate the DNA when the cell divides."

Explain how nucleosomes help DNA to adopt a highly-compact structure while also keeping the DNA molecule accessible for transcription and replication?

Answer 1

in eukaryotes, the nucleosome is the basic structural unit of DNA packaging. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundamental subunit of chromatin. Each nucleosome is composed of a little less than two turns of DNA wrapped around a set of eight proteins called histones, which are known as a histone octamer. Each histone octamer is composed of two copies each of the histone proteins H2A, H2B, H3, and H4. Nucleosome positions in the genome are not random, and it is important to know where each nucleosome is located because this determines the accessibility of the DNA to regulatory proteins.

The nucleosomes coil and stack together to form fibers called chromatin.Compact states of the arrays allow binding to DNA within the central nucleosome via site exposure. Nucleosomes themselves are highly dynamic, spontaneously undergoing “site exposure” conformational fluctuations that make their wrapped DNA transiently accessible to diverse DNA binding proteins

The double helix of DNA is highly negatively charged due to all the negatively charged phosphates in the backbone. DNA can be further packaged by forming coils of nucleosomes, called chromatin fibers. These fibers are condensed into chromosomes during mitosis, or the process of cell division.

Nucleosomes can slide along DNA. When nucleosomes are spaced closely together (top), transcription factors cannot bind and gene expression is turned off. When the nucleosomes are spaced far apart (bottom), the DNA is exposed. Transcription factors can bind, allowing gene expression to occur.

The acetylation of histones is known to increase the expression of genes through transcription activation. By deacetylating the histone tails, the DNA becomes more tightly wrapped around the histone cores, making it harder for transcription factors to bind to the DNA.

After the new strand of DNA is synthesized by the polymerase, assembly factors reconstitute old nucleosomes and assemble new nucleosomes behind the replication fork. Because there is a doubling of genetic material during replication, cells require double the amount of the genome packing material, namely, the histones