

Thomas Jefferson University team shifts a longstanding paradigm for epigenetic marks



“Essentially, all histones are going away during DNA replication and new histones, which are not modified, are coming in,” said Alexander M. Mazo, Ph.D., professor of Biochemistry and Molecular Biology at Jefferson, and a member of Jefferson’s Kimmel Cancer Center. “In other words, what we found is that histone modifying proteins are hiding on the way over replicating DNA, instead of histones ‘jumping’ over as currently thought.”

“What this paper tells us,” he continues, “is that these histone modifying proteins somehow are able to withstand the passage of the DNA replication machinery. They remained seated on their responsive binding sites, and in all likelihood they will re-establish histone modification and finalize the chromatin structure that allows either activation or repression of the target gene.”



According to widely-accepted models applied today, the tails of methylated histones turn genes in DNA “on” or “off” by loosening or tightening nucleosome structure, thus changing the accessibility of transcription factors and other proteins to DNA.

“People believe that everything gets worked off of DNA during the replication process and that these methylated histones act as epigenetic marks, since they are believed to rapidly jump from parental to daughter DNA,” said Dr. Mazo. “But there is no experimental evidence to back this up.”







Published: 08-28-2012

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