Histone ‘map’ yields key insights into fat cell formation

WASHINGTON - Scientists have created a “map” of histone modifications in fat cells, which led them to discover two new factors that regulate fat formation- a key step on the road to better understanding obesity, diabetes and other metabolic disorders.

Investigators at Beth Israel Deaconess Medical Center (BIDMC) and the Broad Institute, led the study.

“These findings help to demonstrate the power of epigenomic mapping when it comes to gleaning key insights into fat cell formation,” explained senior author Dr. Evan Rosen.

To better understand how fat cells, also called 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’. 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,” explained Rosen.

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 cell development, 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 genome. 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. 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,” explained Rosen.

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. 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,” explained Rosen.

The study appears in the latest issue of the journal Cell. (ANI)