Drosophila TRF2 and TAF9 regulate lipid droplet size and phospholipid fatty acid composition

• Published in: PLoS genetics Vol. 13; no. 3; p. e1006664
• Main Authors: Fan, Wei, Lam, Sin Man, Xin, Jingxue, Yang, Xiao, Liu, Zhonghua, Liu, Yuan, Wang, Yong, Shui, Guanghou, Huang, Xun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.03.2017; Public Library of Science (PLoS)
• Subjects: Adipocytes; Alleles; Amino Acid Motifs; Animals; Apoptosis; Biology and Life Sciences; Colleges & universities; Dementia; Developmental biology; Droplets; Drosophila; Drosophila - genetics; Drosophila - metabolism; Drosophila Proteins - metabolism; Fat body; Fatty acids; Fatty Acids - chemistry; Genes; Genetic aspects; Genetics; Genomes; Homeostasis; Insects; Interdisciplinary aspects; Laboratories; Lipids; Lipids - chemistry; Mathematics; Metabolism; Mutation; Oxygen - chemistry; Peroxisomes - chemistry; Phenotype; Phospholipids; Phospholipids - chemistry; Proteins; Research and Analysis Methods; RNA Interference; RNA polymerase; Roles; Sequence Analysis, RNA; Systems science; TATA-binding protein; TATA-Binding Protein Associated Factors - metabolism; Telomeric Repeat Binding Protein 2 - metabolism; Transcription Factor TFIID - chemistry; Transcription Factor TFIID - metabolism; Transcription factors; Beijing China; China
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1006664

The general transcription factor TBP (TATA-box binding protein) and its associated factors (TAFs) together form the TFIID complex, which directs transcription initiation. Through RNAi and mutant analysis, we identified a specific TBP family protein, TRF2, and a set of TAFs that regulate lipid droplet (LD) size in the Drosophila larval fat body. Among the three Drosophila TBP genes, trf2, tbp and trf1, only loss of function of trf2 results in increased LD size. Moreover, TRF2 and TAF9 regulate fatty acid composition of several classes of phospholipids. Through RNA profiling, we found that TRF2 and TAF9 affects the transcription of a common set of genes, including peroxisomal fatty acid β-oxidation-related genes that affect phospholipid fatty acid composition. We also found that knockdown of several TRF2 and TAF9 target genes results in large LDs, a phenotype which is similar to that of trf2 mutants. Together, these findings provide new insights into the specific role of the general transcription machinery in lipid homeostasis.