Sharing MCB Science – Unraveling the relationship between DNA winding and chromatin topology

A 3D model of DNA wrapped around nucleosomes

A model of circular nucleosome array

Cells tackle the complex task of packaging all their DNA into a tiny nucleus by spooling it around nucleosomes, sets of 8 specialized proteins called histones. Historically there has been variation in estimates in the number of times that DNA winds around each nucleosome. This number is known from x-ray crystallography to be about 1.7 superhelical turns; however, previous examination of circular nucleosome arrays indicated to researchers that the number of turns is closer to one. The Grigoryev lab at Pennsylvania State University has proposed an explanation.

Through a more direct approach using a combination of electrophoresis and electron microscopy, Dr. Grigoryev and his lab, in collaboration with Dr. Zhurkin lab at NIH, discovered that the number of turns and the space between nucleosomes is actually quite variable within the same segment of DNA. Furthermore, the distance between nucleosomes seems to influence the number of turns DNA makes per each nucleosome. They also noted that this variability of chromosome spacing could be a mechanism which chromatin domains use to control DNA packing. The findings were published in Science Advances.

DNA packs tightly to fit into the cell nucleus, but how dense it is and how the density is distributed across the genome also influences higher level organization such as chromatin shape and even chromosome shape and structure. Shape and structure, in turn, influence how DNA interacts with the environment around it. For example, the density of DNA-packing influences whether regulatory proteins can properly interact with a gene and therefore whether the gene is expressed. Understanding the mechanisms behind how these changes are managed can provide a better look into how DNA functions, which can expand our ability to understand and manipulate genetic processes.

This work was funded by the Genetic Mechanisms cluster of the Division of Molecular and Cellular Biosciences, award #1516999.

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