Forcing chromosomes into loops may switch off sickle cell disease

Rebecca Morse
Author: -
Published: August 14th, 2014
Link: http://www.sciencedaily.com/releases/2014/08/140814123424.htm

Summary: This article explains how scientists have altered red blood cells, causing them to produce fetal hemoglobin, which is not affected by sickle cell disease (SCD). Hematologists have observed that patients with the disease who have higher levels of fetal hemoglobin than adult hemoglobin experience a more moderate form of SCD. The scientists in this particular article, led by Gerd A. Blobel, forced chromatin to form looped structures that could activate hemoglobin-regulating genes. He and his team had previously adapted zinc fingers that could attach to specific DNA sites which were located far apart on a chromosome. This caused a chromatin loop to form that could convey regulatory signals to certain genes. Another key piece of information the scientists needed for their experiment was that once a child is born, a "biological switch" transitions the blood cells from containing fetal hemoglobin to adult hemoglobin, silencing the genes that produce the former. Knowing that adult hemoglobin in people with SCD leads to misshapen cells that can damage organs and clog up blood vessels, Blobel and his team designed zinc fingers to flip the "biological switch" in cells that produced blood. It reactivated the genes that expressed fetal hemoglobin while simultaneously deactivating the genes that expressed adult hemoglobin. Blobel and his team got their results by using cultured blood cells taken from adult humans and adult mice. He speculates that forcing chromatin looping could also be applied to other disorders pertaining to hemoglobin.

Connection: This article relates to topics we have covered throughout this term in a couple different ways. Firstly, in chapter 11 of our science textbook, we learned about genetics and how a mutation is any change in the nucleotide sequences contained in DNA, ranging from big regions of a chromosome to a single nucleotide pair. In the case of sickle cells, the mutation is caused by one nucleotide in a sequence consisting of 438 bases. The textbook, in both chapters 11 and 14, wrote about how this mutation led to cells forming a sickle-shape that could block tiny blood vessels and in turn, the flow of blood, just as written about in the article above. Additionally in our studies of genetics, we learned how some diseases cannot be inherited, like cancers, while others can, like the SCD. In chapter 13, we studied how genes could be turned on and off. Lactose, for example, could be made when a repressor molecule did not bind to the operator; however, when lactose was not present, the repressor would bind to the operator, halting production. This is somewhat similar to how the scientists used zinc fingers that coil the chromatin to activate the genes that produced fetal hemoglobin and deactivate the genes producing adult hemoglobin. Both mutations in genes causing sickle cell disease and how genes are turned on and off were detailed in our course in this past term, and both of these topics were covered in the article.