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Probing matters of the heart
Date:9/14/2012

istone-modification patterns shift rapidly as a stem cell differentiates. Furthermore, the patterns reveal genes that are active at different stages, as well as regulatory elements that control those genes.

Tracking development

To discover those patterns, the researchers grew mouse embryonic stem cells in a lab dish and treated them with proteins and growth factors that drive heart cell development. The cells could be followed through four distinct stages, from embryonic stem cells to fully differentiated cardiomyocytes (the cells that compose heart muscle). At each stage, the researchers used high-throughput sequencing technology to analyze histone modifications and determine which genes were being expressed.

"It's basically watching differentiation over time in a dish, and being able to take snapshots of that and put it all together to try to understand how the complex process of cardiac commitment is regulated," Boyer says.

The researchers found that they could identify groups of genes with related functions by comparing their modification patterns and whether they were being transcribed at a particular time. They also identified regulatory regions located far away from the genes they regulate. Many of these regions were located in sections of DNA previously thought to be "junk." Recent studies have revealed that much of this DNA actually plays important roles in regulating gene expression.

"We're starting to link genes with the regulatory elements that may be activating them, and beginning to draw a picture of the molecular circuitry that is controlling and driving these cardiac-specific programs the DNA elements that are important for turning on all the genes that you need to make a heart cell," Wamstad says.

The team also identified transcription factors proteins that initiate the expression of genes that appear to work collaboratively at regulatory regions to drive transcription of genes importan
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Contact: Sarah McDonnell
s_mcd@mit.edu
617-253-8923
Massachusetts Institute of Technology
Source:Eurekalert

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