Chromatin Speaks! Cell Signal Receiver also Found To Transmit

A blend of histone proteins and DNA that packs genes into chromosomes, chromatin influences gene expression, DNA repair and chromosome recombination.

Scientists at The University of Texas MD Anderson Cancer Center, writing this week in the journal Cell, have identified another function - signaling molecule. Chromatin is on the receiving end of signaling pathways that turn genes off and on, but research by Sharon Dent, Ph.D., and colleagues found that chromatin talks back.

"It's a basic change in our way of thinking about cell signaling - that all signals go into the nucleus and dead-end at DNA, that they point to chromatin and stop," says Dent, professor and chair of MD Anderson's Department of Molecular Carcinogenesis and director of its Center for Cancer Epigenetics.

"Our data show that's not the case. We have a new fundamental aspect of cellular regulation that we need to now explore," Dent says.

In a series of yeast experiments, Dent and colleagues show that a signal through a histone protein regulates another protein called Dam1 that is involved in the separation of chromosomes during cell division.

The crucial step is the attachment of a single signaling molecule called ubiquitin to a histone protein called H2B. This event was known to direct addition of methyl groups to histone H3, but Dent's work indicates it is also required for methylation of Dam1.

Communication between H2B and Dam1 is the first such instance of cross-talk between histone and non-histone proteins, the authors report. The signaling connection between a chromatin change and a non-DNA-templated process such as chromosome separation is also new.

Connections between histone ubquitination and histone methylation also occur in human cells, and mutations in a protein highly related to Set1, called MLL, are involved in leukemia. Dent's work raises the possibility that histones can signal to non-histone proteins in human cells and that mismanagement of these events caused by MLL mutations might contribute to leukemia development.

Resources News release-UT MD Anderson Scientists Discover Secret Life of Chromatin

The Cell paper: Chromatin Signaling to Kinetochores