Changes to the structure of the histone variant H3.3 may play a key role in silencing genes that regulate cancer cell growth, according to a study led by researchers from the Icahn School of Medicine, Mount Sinai Hospital, in New York City. The results were published online on November 14, 2014 in Nature Communications. According to the authors, this is the first study to identify H3.3 as a key regulator in cellular senescence, a process in which cells stop multiplying. Cellular senescence has garnered significant scientific interest lately because it may be one key to prevent the initiation of cancer. However, little is known about this process and how genes that enable cells to divide and multiply (the cell cycle) are turned off. A growing body of evidence suggests that the process of cellular senescence is driven by changes in the protein complexes called chromatin in the nuclei of cells. Using models of senescence, researchers found that histone variant H3.3, a protein that works closely with chromatin to package and regulate genetic material within cells, and, in particular, the clipped form of this protein, H3.3cs1, help to silence target genes that regulate the cell cycle. Could the presence of this protein stop cells from dividing? Indeed, using genome-wide transcriptional profiling, the researchers discovered that expression of clipped H3.3 (i.e., 3.3cs1) silences genes that regulate the division and duplication of a cell. "Cellular senescence creates a chromatin environment that represses cell multiplication, and thus cell or tumor growth, but how this happens molecularly is what we sought to discover," said lead investigator Emily Bernstein, Ph.D., Department of Oncological Sciences, Icahn School of Medicine, Mount Sinai Hospital.
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