Daily Archives: December 14, 2012

Study explores the boundaries of embryonic development (eLife)

If all of the DNA in a human cell was stretched out, it would be about two meters long. The nucleus of a human cell, on the other hand, has a diameter of just 6 micrometers, more than 300,000 times smaller, so the DNA molecules that carry all the genetic information in the cell need to be carefully folded to fit inside the nucleus. Cells meet this challenge by combining their DNA molecules with proteins to form a compact and highly organized structure called chromatin. Packaging DNA into chromatin also reduces damage to it.

But what happens when the cell needs to express the genes carried by the DNA as proteins or other gene products? The answer is that the compact structure of chromatin relaxes and opens up, which allows the DNA to be transcribed into messenger RNA. Indeed, packing DNA into chromatin makes this process more reliable, thus ensuring that the cell only produces proteins and other gene products when it needs them. However, because cross-talk between neighboring genes could potentially disrupt or change gene expression patterns, cells evolved special elements called boundaries or insulators to stop this from happening. These boundary factors divide the chromosomes into subdomains that can function independently of each other.

Since the protein factors implicated in boundary function seemed to be active in all tissues and cell types, it was assumed for many years that these boundaries and the resulting chromatin domains were fixed. However, a number of recent studies have shown that boundary activity can be subject to regulation, and thus chromatin domains are dynamic structures that can be defined and redefined during development to alter patterns of gene expression.

New research from the laboratory of Paul Schedl at Princeton University has uncovered a new fruit fly boundary factor that, unlike previously characterized factors, is active only during a specific stage of development. The Elba factor is also unusual in that it is made of three different proteins, known as Elba1, Elba2, and Elba3, and all three must be present for it to bind to DNA. The lead author of the study was Tsutomo Aoki of the Princeton University Department of Molecular Biology. Aoki worked with co-authors Ali Sarkeshik and John Yates from the Scripps Research Institute in La Jolla, CA.

While Elba2 is present during most stages of development, the other two Elba proteins are only present during early embryonic development, so the boundary factor is only active in early embryos. In addition to revealing a new mechanism for controlling boundary activity as an organism develops, the studies of Aoki et al. provide further evidence that chromatin domains can be dynamic.

Aoki, Tsutomu, Ali Sarkeshik, John Yang, and Paul Schedl. Elba, a novel developmentally regulated chromatin boundary factor is a hetero-tripartite DNA binding complex. eLife 2012;1:e00171

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Article summary provided by eLife.