title: A Krüppel-like factor in Caenorhabditis elegans with essential roles in fat regulation, cell death, and phagocytosis.
abstract: We demonstrate that a Caenorhabditis elegans Krüppel-like transcription factor is involved in fat regulation, cell death, and phagocytosis in C. elegans. Suppression of C. elegans klf-1 function by RNA interference (RNAi) results in increased fat storage in the intestine of the RNAi worm that directly or indirectly causes germ cells to die. These dead cells are not engulfed or phagocytosed in the RNAi worm. High-level expression of Ce-klf-1 during larval development, as well as its specific localization in the worm's intestine, supports a direct role for Ce-klf-1 in fat regulation. The C. elegans klf-1 encodes a C(2)H(2) zinc finger protein that is known to act as transcriptional modulator of tissue-specific expression. Members of the Krüppel-like factor (KLF) family play a variety of important roles in vertebrate tissue differentiation. KLFs have recently been implicated in energy and glucose homeostasis through their expression in pancreas, adipose, liver, and muscle tissues. The extensive fat storage and increased cell death in the Ce-klf-1 RNAi worm is important in that it may explain the connection between Ce-klf-1 signaling, cell death, and fat storage. This is the first evidence involving Ce-KLF-1 protein in such functions. In future studies, a thorough analysis of cellular functions of other members of C. elegans Krüppel-like transcription factors together with their interactions and pathway activities with other molecular partners should yield significant insights into mammalian KLF proteins.
authors.affiliation: Laboratories of Developmental Biology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USA. shashmi@nybloodcenter.org
authors.forename: Sarwar
authors.initials: S
authors.lastname: Hashmi
authors.forename: Qiongmei
authors.initials: Q
authors.lastname: Ji
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Ranjit S
authors.initials: RS
authors.lastname: Parhar
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Huang
authors.forename: Chris
authors.initials: C
authors.lastname: Brey
authors.forename: Randy
authors.initials: R
authors.lastname: Gaugler
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D010587:Phagocytosis / Q000502:physiology*; D034622:RNA Interference; D018510:RNA, Helminth / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D019076:Transgenes / Q000502:physiology; D016335:Zinc Fingers
chemical_list: D029742:Caenorhabditis elegans Proteins; C532590:Klf-1 protein, C elegans; D051741:Kruppel-Like Transcription Factors; D018510:RNA, Helminth; D049452:Green Fluorescent Proteins