TY - JOUR T1 - Intronic Cis-Regulatory Modules Mediate Tissue-Specific and Microbial Control of angptl4/fiaf Transcription A1 - Camp, J. Gray A1 - Jazwa, Amelia L. A1 - Trent, Chad M. A1 - Rawls, John F. Y1 - 2012/03/29 N2 - Author Summary Recent studies have revealed that the community of microorganisms residing in the intestine regulates fat storage. Microbes evoke this response in part by suppressing expression of the Angptl4 gene, which encodes a secreted inhibitor of fat storage. Although Angptl4 is expressed in multiple tissues, microbial suppression occurs only in the intestine. To determine how microbes control fat storage, we must elucidate the mechanisms underlying intestine-specific and microbial regulation of Angptl4 expression. Here, we take advantage of the unique features of the zebrafish model to define the regulatory DNA sequences controlling angptl4 expression. Our results reveal that different DNA regulatory regions within the angptl4 gene mediate expression of angptl4 in the intestine and other tissues. By assessing the evolution of angptl4 regulatory regions and subjecting them to structure-function analyses, we identify discrete DNA sequences that are required for intestinal expression. Strikingly, microbes suppress the activity of the intestine-specific regulatory region similar to the endogenous angptl4 gene. Therefore, intestinal microbes might regulate angptl4 production by suppressing the signaling pathway interpreted by an intestine-specific transcriptional regulatory region. Our results provide new mechanistic insights into how intestinal microbes might influence fat storage and contribute to the development of obesity. JF - PLOS Genetics JA - PLOS Genetics VL - 8 IS - 3 UR - https://doi.org/10.1371/journal.pgen.1002585 SP - e1002585 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pgen.1002585 ER -