By Sharon Dent, Ph.D., David Johnson, Ph.D., and Sarah Adai

Chromatin, the intertwined histone proteins and DNA that are packaged into chromosomes, has long been recognized as a gatekeeper to the underlying DNA template.

While chromatin is typically on the receiving end of the cell's intricate signaling pathways - culminating in the regulation of gene expression - evidence is emerging to give chromatin a previously unrecognized role: as a dynamic participant that transmits received signals back to other proteins to effect changes in cellular responses.  

This week in the journal Cell, faculty from MD Anderson's Department of Molecular Carcinogenesis and Center for Cancer Epigenetics review a number of recent studies highlighting chromatin's role as both receiver and transmitter of signals in various cell functions.

Histone modifications: key players in chromatin signaling

Posttranslational modification of histones is one way that the cell regulates the packing and unpacking of chromatin, which in turn helps to determine whether a gene is activated or repressed.

When a crucial enzyme is dotted with targets that summon an attack by a cell's protein-destroying complex, another molecule comes to the rescue, blinding the attacker by wiping off the targets. 

The enzyme, called TRAF3,  survives to control a molecular network that's implicated in a variety of immune system-related diseases if left to its own devices.

University of Texas MD Anderson Cancer Center scientists identified TRAF3's savior and demonstrated how it works in a paper published online this week in Nature.

By discovering the role of OTUD7B as TRAF3's protector, Shao-Cong Sun, Ph.D., professor in MD Anderson's Department of Immunology, and colleagues filled an important gap in their understanding of a molecular pathway discovered in Sun's lab.

"Genetic defects or constant degradation of TRAF3 lead to the uncontrolled activity of what we call the non-canonical NF-kB pathway. This in turn, is associated with autoimmune diseases and lymphoid malignancies such as multiple myeloma and B cell lymphomas," Sun said. "Understanding how the degradation of TRAF3 is regulated is extremely important."

Cancer begins when a single cell goes haywire.  Now the keys to understanding that cell's transition to lethal tumor may be found in the unprecedented analysis of single tumor cells.

By isolating, capturing and then analyzing the genome of individual cells, Nicholas Navin, Ph.D., assistant professor in MD Anderson's Department of Genetics, proposes to identify the mutations that allow a primary tumor cell to escape into the bloodstream and then to establish a deadly colony in another organ.

Successfully analyzing differences in active mutations among single cells would help researchers understand, map and eventually block the lethal path to metastasis - the spread of the primary cancer to other organs.  Primary tumors are rarely lethal, Navin notes, but their genetic diversity from cell to cell hinders scientists' ability to understand metastasis.

The Damon Runyon Cancer Research Foundation will give Navin the opportunity to try his unique approach.  He is the Nadia's Gift Foundation Innovator, one of only seven 2013 Damon Runyon-Rachleff Innovation Awards announced earlier this month.

The foundation announcement notes the innovation awards are for "cancer research by exceptionally creative thinkers with "high-risk/high-reward" ideas who lack sufficient preliminary data to obtain traditional funding." Navin's approach "will have myriad clinical applications, which have prognostic value in predicting invasion, metastasis, survival and response to chemotherapy."