Untangling DNA regulation

November 06, 2008

CAMBRIDGE, Mass. -- MIT biologists have discovered that the organization of DNA's packing material plays a critical role in directing stem cells to become different types of adult cells.

The work, to be published in the journal Cell on Nov. 14, could also shed light on the possible role of DNA packaging in cancer development.

Led by Laurie Boyer, assistant professor of biology at MIT, the researchers examined the role of chromatin -- the structure that forms when DNA is wound around a core of proteins called histones.

"We're particularly interested in how chromatin structure influences gene expression and ultimately cell fate," Boyer said. "We hope the studies we are doing can lead to better understanding of development as well as certain diseases."

It has been theorized that cancer cells may overexpress genes involved in early embryonic development, allowing them to proliferate unchecked and regress from adult tissue cells to a stem cell-like state.

Such regression could be partly mediated by changes in chromatin. This packaging is believed to help control DNA transcription because the more tightly wound the chromatin is, the less accessible DNA is to be transcribed.

The new study focused on a variant type of histone known as H2AZ, which other researchers have recently identified as a protein of interest in cancer.

While H2AZ is ubiquitously expressed in many cell types including adult cells, it is known to be essential for normal embryonic development. The new research reveals why: The variant histones are found near the promoter regions of a particular set of genes that are important for development.

The same genes are also regulated by a group of proteins known as Polycomb group (PcG) proteins, which act as gene silencers.

"It suggests that this histone variant -- along with the Polycomb group proteins -- may act as some kind of regulatory switch that mediates cell fate transitions," Boyer said. "We hypothesize that they're working together, and that allows these genes to be silent yet poised for activation in stem cells."

In future studies, Boyer's team plans to look at patterns of H2AZ distribution in cancerous cells.
-end-
Lead authors of the paper are Whitehead Institute postdoctoral associates Menno Creyghton and Styliani Markoulaki. Other authors are Whitehead postdoctoral associates Stuart Levine and Jacob Hanna; graduate student Michael Lodato; Ky Sha, a postdoctoral associate in biology; Richard Young, professor of biology; and Rudolf Jaenisch, professor of biology and member of the Whitehead Institute.

The research was funded by the Dutch Cancer Foundation, the Helen Hay Whitney Foundation, the National Institutes of Health and Genzyme Corp.

By Anne Trafton, MIT News Office

Massachusetts Institute of Technology

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.