Spool-like proteins called histones play a crucial role in packaging the nearly seven feet of DNA found in most human cells. A new study shows that a group of histones that are thought to behave the same way actually are functionally distinct proteins.
The findings by researchers at the Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) indicate that replication-dependent histone isoforms can have distinct cellular functions, and that changes in expression of the various isoforms might play a role in cancer development.
The study is published in the journal Nucleic Acids Research as a Breakthrough Article, placing it among the top 2-3 percent of papers presented by the journal in terms of significance and excellence.
"Replication-dependent histone isoforms have always been thought to be functionally identical, but we show that they have distinct functions, and that altering the levels of these isoforms can influence cell proliferation and tumor development," says principal investigator Mark Parthun, PhD, professor of Molecular and Cellular Biochemistry and a member of the OSUCCC - James Experimental Therapeutics Program.
"These highly novel results provide a new mechanism for the regulation of chromatin structure, Parthun says."
Replication-dependent histones are highly expressed just before the onset of DNA replication during the cell cycle, and they are repressed when DNA replication is completed.
The genes that encode these histones are located in large clusters that can contain dozens of histone genes. "This localization in gene clusters led to the belief that these histones are regulated as a group, and that the multiple genes encoding each histone are functionally equivalent," Parthun says.