ROLE OF MACROH2A HISTONES IN REGULATING ANIMAL METABOLISM AND ENDOGENOUS RETROVIRUSES

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: ANIMAL HEALTH
• Reporting Frequency: Annual
• Accession No.: 0209662
• Project Start Date: Oct 1, 2006
• Project End Date: Sep 30, 2007
• Program Code: [(N/A)]- (N/A)

Recipient Organization
UNIV OF PENNSYLVANIA
(N/A)
PHILADELPHIA,PA 19104

Performing Department
SCHOOL OF VETERINARY MEDICINE

Non Technical Summary
Optimal metabolic balance is critical to the health and growth of all animals, including livestock and poultry. We are conducting basic research on molecular mechanisms that regulate animal metabolism and control the expression of endogenous retroviruses.

Animal Health Component

100%

Research Effort Categories

Basic

(N/A)

Applied

100%

Developmental

(N/A)

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
311	3999	1040	100%

Knowledge Area
311 - Animal Diseases;

Subject Of Investigation
3999 - Animal research, general;

Field Of Science
1040 - Molecular biology;

Keywords

metabolism

endogenous

retrovirus

histones

Goals / Objectives
The objective of this project is to identify the molecular defects that underlie the metabolic and other effects we have observed in macroH2A1/2 double knockout mice.

Project Methods
We plan to focus on genome wide studies ofgene expression to identify genes that have altered expression in macroH2A1/2 double knockout mice in comparison to control mice. This analysis should allow us toidentify many of the genes that are being regulated by macroH2A histones. Since we believe that most and possibly all effects of macroH2As are related to theireffects on the gene expression, these studies should help provide a basic foundation for understanding howmacroH2As alter metabolism. We will also investigate the expression of endogenous retroviruses in double knockouts, as macroH2A1 and macroH2A2 histone variants may cooperate in restricting the expression of endogenous retroviruses.

Progress 10/01/06 to 09/30/07

Outputs
OUTPUTS: The major activities supported by this grant involved laboratory research on mice that are genetically to have knockout mutations in the genes encoding macroH2A1 histone variants. The funds helped to pay part of the salary for a Research Specialist (Geetika Singh) and for supplies to do the work. PARTICIPANTS: Funding supported part of the salary of Geetika Singh, a Research Specialist who worked on the project. Ms. Singh had recently graduated with a Masters in Biotechnology from the University of Pennsylvania. This project helped her to develop both technical and theoretical laboratory research skills. TARGET AUDIENCES: The target audiences for this research are basic biomedical research communities interested in epigenetic mechanisms of controlling genes expression and those interested in endogenous retroviruses and other retrotransposons that populate animal genomes. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
The funded studies helped to demonstrate that macroH2A1 histone variants have an important role in repressing the expression of endogenous murine leukemia viruses in the mouse. Endogenous retroviruses such as these can form infectious viruses that mutate the genome and cause diseases including cancer and immunodeficiency disorders. Repressing the expression of these elements helps to reduce their potential for causing disease.

Publications

• Changolkar, L.N., Singh, G. and Pehrson, J.R. macroH2A1-mediated silencing of endogenous murine leukemia viruses. Mol. Cell. Biol., 28, 2059-2065, 2008.