A heart muscle cell functions differently from a bone cell or a cancerous cell, yet inside each is an identical set of DNA arranged into genes. What makes one cell type different from another is the unique profile of genes that are turned on ('expressed') or off at any given moment. While the control of gene expression is one of the key gatekeepers to the specialization of normal cells, little is known about how the three-dimensional organization of DNA affects this complex process.
PM Cancer Centre Scientist Dr. Mathieu Lupien has uncovered a protein that helps fold DNA to control the expression of specific genes. The protein, ZNF143, creates a physical connection between a specific gene and a distant regulatory element. The resulting three-dimensional structure, called a chromatin loop, sets the overall DNA architecture enabling specific genes to be expressed.
“The ZNF143 protein associates with different genes in different cell types, and thus provides different folding instructions to the DNA. This enables the cells to express the specific gene profile that helps them perform their unique functions,” explains Dr. Lupien. “Our study also shows that changes to the DNA sequence can alter this process and cause abnormal chromatin loop formation, which may lead to disease development.”
This work was supported by the National Institutes of Health, the Ontario Institute for Cancer Research, the Canadian Institutes of Health Research and The Princess Margaret Cancer Foundation.
ZNF143 provides sequence specificity to secure chromatin interactions at gene promoters. Bailey SD, Zhang X, Desai K, Aid M, Corradin O, Cowper-Sal Lari R, Akhtar-Zaidi B, Scacheri PC, Haibe-Kains B, Lupien M. Nature Communications. 2015 Feb 3. [Pubmed abstract]
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