Epigenomics discovery yields new information about fat cells

September 30, 2010

By creating a "map" of histone modifications in fat cells, investigators have discovered two new factors that regulate fat formation, a key step on the road to better understanding obesity, diabetes and other metabolic disorders. Led by investigators at Beth Israel Deaconess Medical Center (BIDMC) and the Broad Institute, the study appears in the October 1 issue of the journal Cell.

"These findings help to demonstrate the power of epigenomic mapping when it comes to gleaning key insights into fat ," explains senior author Evan Rosen, MD, PhD, an investigator in the Department of Endocrinology, Diabetes and Metabolism at BIDMC and Associate Professor of Medicine at Harvard Medical School. , also called adipocytes, play an integral role in regulating metabolism by controlling and glucose balance.

To better understand how adipocytes control the genes that impart the specialized functions of these cells, the researchers turned to epigenomics, and specifically the arm of epigenomics known as histone modifications.

"Deoxyribonucleic acid [DNA] is tightly wound around proteins called histones, which, over time, can accumulate chemical modifications or 'marks,'" explains Rosen. "These marks instruct the cell which genes to turn on and off, and by mapping these modifications, we can gain important insights that would be unattainable through traditional means."

Unlike previous investigations, which examined fat cells at a single static time point, this new study mapped several histone modifications throughout the course of the fat , using a technique called chromatin immunoprecipitation followed by massively parallel sequencing or ChIP-Seq. This method relies on the ability to sequence tens of millions of short stretches of DNA (in this case DNA bound to modified histones) and then to reassemble results into a coherent . In addition to following these histone markers across time, the scientists also mapped the markers across species.

"Our study looked at both mouse cells and human cells," explains Rosen. "This is key because each cell type can accumulate histone marks that actually have nothing to do with fat cell differentiation. Consequently, by comparing two different cell models, we were able to sift through and focus on the epigenetic marks that appeared in both cell types."

What emerged was a "core" set of histone modifications that formed the basis of a "road map" for the scientists to follow. And, by using this new map, the investigators discovered two transcription factors (proteins that control the copying of DNA into RNA) that regulate fat cell formation.

"We found two new transcription factors - SRF and PLZF - involved in fat cell development," explains Rosen. "We have essentially demonstrated how an epigenomic 'road map' can be used to identify biology that could not have been predicted through any other means." Subsequent experiments confirmed the proteins' roles in fat cell development: When either the SRF or the PLZF protein was decreased, fat cells generated at a faster rate and, conversely, when the amount of either protein was increased, fat cell development ceased.

"Although these particular studies were focused on the development of fat cells, we have reason to think that SRF and PLZF may be involved in the workings of mature fat cells as well," notes Rosen, adding that these new findings, therefore, have the potential to impact metabolic diseases such as obesity and Type 2 diabetes.

"The huge costs of obesity and metabolic disease, both in terms of health and from a financial standpoint, are making adipocyte biology increasingly important," he adds. "With these new findings we now have a better understanding of normal fat cell development, and going forward, we can compare normal fat cells to fat cells in disease states. If we can better understand why fat cells behave as they do, then we can work to develop therapies for obesity or diabetes."

Explore further: Human virus makes fat stem cells fatter

Related Stories

Human virus makes fat stem cells fatter

October 25, 2006

U.S. research showing how a human virus targets fat stem cells to produce more, fatter, fat cells is providing insights into the study of obesity.

Fat chance: Brown vs. white fat cell specification

May 14, 2008

In the May 15th issue of G&D, Dr. Bruce Spiegelman (Dana Farber Cancer Institute) and colleagues elucidate the molecular pathway that induces cells to become energy-burning brown fat cells as opposed to energy-storing white ...

Newly identified cells make fat

October 4, 2008

To understand where fat comes from, you have to start with a skinny mouse. By using such a creature, and observing the growth of fat after injections of different kinds of immature cells, scientists at the Howard Hughes Medical ...

Fat-regenerating 'stem cells' found in mice

October 10, 2008

Researchers have identified stem cells with the capacity to build fat, according to a report in the October 17th issue of the journal Cell, a Cell Press publication. Although they have yet to show that the cells can renew ...

Scientists map molecular regulation of fat-cell genetics

November 4, 2008

A research team led by Mitchell Lazar, MD, PhD, Director of the Institute for Diabetes, Obesity, and Metabolism at the University of Pennsylvania School of Medicine, has used state-of-the-art genetic technology to map thousands ...

Regulating fat cell differentiation

June 15, 2010

(PhysOrg.com) -- New research led by University College Dublin Conway Fellow, Professor Johan Ericsson has identified a key regulator of fat cell differentiation that may be a novel target for obesity drugs. The results of ...

Recommended for you

Scientists overcome key CRISPR-Cas9 genome editing hurdle

December 1, 2015

Researchers at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT have engineered changes to the revolutionary CRISPR-Cas9 genome editing system that significantly cut down on "off-target" ...

Study finds 'rudimentary' empathy in macaques

December 1, 2015

(Phys.org)—A pair of researchers with Centre National de la Recherche Scientifique and Université Lyon, in France has conducted a study that has shown that macaques have at least some degree of empathy towards their fellow ...

Which came first—the sponge or the comb jelly?

December 1, 2015

Bristol study reaffirms classical view of early animal evolution. Whether sponges or comb jellies (also known as sea gooseberries) represent the oldest extant animal phylum is of crucial importance to our understanding of ...

Trap-jaw ants exhibit previously unseen jumping behavior

December 1, 2015

A species of trap-jaw ant has been found to exhibit a previously unseen jumping behavior, using its legs rather than its powerful jaws. The discovery makes this species, Odontomachus rixosus, the only species of ant that ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.