Nature: "Magic Scissor" CRISPR is committed to finding a "new drug" for leukemia!
Release date: 2017-03-06
We often need to use employee IDs to enter and leave the workplace, and a protein called ENL in the cell also brings new hope for the treatment of acute myeloid leukemia (AML) in the same way. AML is an invasive blood cancer that affects people of all ages and is the second most common type of leukemia.
A study from the University of Texas MD Anderson Cancer Center found an important role for ENL in the progression of leukemia and pointed out that a class of experimental drugs using BET inhibitors may be effective in treating AML. The research was published in the March 1 issue of the journal Nature. One of the authors of the article is Dr. Xiaobing Shi of the MD Anderson Cancer Center.
For nearly two decades, scientists have come to realize that the genetic code in DNA represents only a part of the information in the life blueprint. Genetic information also comes from specific chemical labeling patterns on DNA structures that determine the tightness of DNA packaging and the switching of specific genes.
In 2014, Shi Xiaobing and the research team of Professor Li Haitao of Tsinghua University found a new class of histone acetylation modified "reader": YEATS domain, the discovery of a new "reader" has been a study in the field of epigenetics. Hot spot. To date, nearly 30 kinds of "readers" have been discovered. Among them, the well-known lysine acetylation reader is the Bromo domain.
The YEATS domain is highly conserved from yeast to humans (including sequence and function), and hundreds of protein members containing the YEATS domain have been identified in more than 70 species, such as AF9, ENL, GAS41, YAF9, SAS5, TAF14, etc., are components of some important epigenetic regulatory complexes (including chromatin remodeling complexes, histone acetylated complexes, etc.).
On this basis, the researchers further discovered that ENL containing the YEATS domain "reader" promotes leukemia progression. "Our research shows that ENL is a component required for AML leukemia maintenance," Dr. Shi said, "ENL is consumed. It triggers an anti-leukemia effect that inhibits the growth of leukemia cells in vitro and in vivo. It is also worth noting that blocking ENL can further lead to sensitization of leukemia cells to BET inhibitors.
Histone modifications such as acetylation can serve as docking sites for the recognition of specific modified reader proteins and can affect downstream biological functions. Although many such histone-modified reading proteins have been identified so far, little is known about histone acetylation.
The latest research uses the CRISPR gene editing tool, which eliminates ENL and inhibits the expression of cancer genes, which can have important effects because cancer cells are often involved in chromatin regulation pathways.
"Targeted epigenetic readers are a very promising anticancer treatment direction," said Dr. Hong Wen, the first author of the paper, assistant professor of epigenetics and molecular carcinogenesis. "Our findings ENL can be used as a chromatin reader to regulate carcinogenic procedures, suggesting that ENL can serve as a potential drug target for AML in the future."
Source: Biopass
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