Features | Partner Sites | Information | LinkXpress
Sign In
JIB
GLOBETECH PUBLISHING
BioConferenceLive

Histone Deacetylase 3 Critical in Maintaining Healthy Intestinal Function

By BiotechDaily International staff writers
Posted on 11 Nov 2013
Image: A histologic section of intestinal tissue isolated from healthy mice stained to visualize intestinal epithelial cells (EpCAM, red), including Paneth cells (lysozyme, magenta), as well as immune cells (CD45, green) Nuclei are stained with DAPI (blue) (Photo courtesy of the University of Pennsylvania).
Image: A histologic section of intestinal tissue isolated from healthy mice stained to visualize intestinal epithelial cells (EpCAM, red), including Paneth cells (lysozyme, magenta), as well as immune cells (CD45, green) Nuclei are stained with DAPI (blue) (Photo courtesy of the University of Pennsylvania).
A team of molecular microbiologists have found that the enzyme HDAC3 (histone deacetylase 3) in intestinal epithelial cells regulates the relationship between commensal bacteria and mammalian intestine physiology.

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation and deacetylation alter chromosome structure and affect transcription factor access to DNA. HDAC3 represses transcription when tethered to a promoter. This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. The HDAC3 gene is regarded as a potential tumor suppressor gene.

Investigators at the University of Pennsylvania (Philadelphia, USA) examined the role of HDAC3 in maintaining a healthy symbiotic relationship between the intestinal tract and its mixture of commensal bacteria—the microbiota.

To this end, the investigators genetically engineered a line of mice that lacked HDAC3 specifically in the intestinal epithelium. They found that these animals exhibited extensive dysregulation of gene expression, including decreased basal expression of genes associated with antimicrobial defense. When housed under normal laboratory conditions, the genetically engineered mice demonstrated loss of Paneth cells (which secrete antibacterial compounds into the lumen of the intestinal gland, thereby contributing to maintenance of the gastrointestinal barrier), impaired gastrointestinal function, and alterations in the composition of intestinal commensal bacteria. In addition, HDAC3-deficient mice showed significantly increased susceptibility to intestinal damage and inflammation.

Normal gastrointestinal behavior was maintained if the HDAC3-deficient mice were raised in a germ-free environment so that they lacked commensal bacteria.

“There is a fundamental change in the relationship between commensal bacteria and their mammalian hosts following deletion of HDAC3 in the intestine,” said senior author Dr. David Artis, associate professor of microbiology at the University of Pennsylvania. “The implication is that intestinal expression of HDAC3 is an essential component of how mammals regulate the relationship between commensal bacteria and normal, healthy intestinal function. Obviously more has to be done, but it is clear that this is a pathway that is of significant interest as we continue to define how mammals have coevolved with beneficial microbes.”

The study was published in the November 3, 2013, online edition of the journal Nature.

Related Links:

University of Pennsylvania



comments powered by Disqus

Channels

Drug Discovery

view channel
Image: Molecular rendering of the crystal structure of parkin (Photo courtesy of Wikimedia Commons).

Cinnamon Feeding Blocks Development of Parkinson's Disease in Mouse Model

A team of neurological researchers has identified a molecular mechanism by which cinnamon acts to protect neurons from damage caused by Parkinson's disease (PD) in a mouse model of the syndrome.... Read more

Therapeutics

view channel

Vaccine Being Developed for Heart Disease Close to Reality

The world’s first vaccine for heart disease is becoming a possibility with researchers demonstrating significant arterial plaque reduction in concept testing in mice. Klaus Ley, MD, from the La Jolla Institute for Allergy and Immunology (LA Jolla, CA, USA), and a vascular immunology specialist, is leading the vaccine... Read more

Business

view channel

A Surge in IPOs Revitalize Investments for the Global Pharma and Biotech

Anti-infective drugs, oncology, and pharmaceutical contract laboratories attract the most investment up to now. The intensified private equity and venture capital (PEVC) deal activity in the global healthcare industry during the recession years, 2008–2010, witnessed a waning post-2010. However, the decline in deals... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.