title: A chromatin modifier integrates insulin/IGF-1 signalling and dietary restriction to regulate longevity.
abstract: Insulin/IGF-1-like signalling (IIS) and dietary restriction (DR) are the two major modulatory pathways controlling longevity across species. Here, we show that both pathways license a common chromatin modifier, ZFP-1/AF10. The downstream transcription factors of the IIS and select DR pathways, DAF-16/FOXO or PHA-4/FOXA, respectively, both transcriptionally regulate the expression of zfp-1. ZFP-1, in turn, negatively regulates the expression of DAF-16/FOXO and PHA-4/FOXA target genes, apparently forming feed-forward loops that control the amplitude as well as the duration of gene expression. We show that ZFP-1 mediates this regulation by negatively influencing the recruitment of DAF-16/FOXO and PHA-4/FOXA to their target promoters. Consequently, zfp-1 is required for the enhanced longevity observed during DR and on knockdown of IIS. Our data reveal how two distinct sensor pathways control an overlapping set of genes, using different downstream transcription factors, integrating potentially diverse and temporally distinct nutritional situations.
authors.affiliation: Molecular Aging Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Anupama
authors.initials: A
authors.lastname: Singh
authors.affiliation: Molecular Aging Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Kumar
authors.affiliation: CSIR-Institute of Genomics & Integrative Biology, South Campus, Mathura Road, New Delhi, 110020, India.|Academy of Scientific and Innovative Research, CSIR-IGIB, Mathura Road Campus, New Delhi, India.
authors.forename: Latika
authors.initials: L
authors.lastname: Matai
authors.affiliation: Molecular Aging Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Jain
authors.affiliation: Molecular Aging Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Garg
authors.affiliation: Molecular Aging Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Arnab
authors.initials: A
authors.lastname: Mukhopadhyay
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D031204:Caloric Restriction; D002843:Chromatin / Q000378:metabolism*; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D007328:Insulin; D020033:Protein Isoforms; D014157:Transcription Factors; C579560:Zfp-1 protein, C elegans; D007334:Insulin-Like Growth Factor I
keywords: C. elegans; daf-16; dietary restriction; incoherent feed-forward loop; insulin signalling; lifespan; pha-4; zfp-1