Lifespan extension and increased pumping rate accompany pharyngeal muscle‐specific expression of nfi‐1 in C. elegans

Abstract

Caenorhabditis elegans nfi-1 belongs to the Nuclear Factor I (NFI) family of transcription factors known to regulate metazoan gene expression and development. We showed previously that loss of nfi-1 in worms results in multiple behavioral defects; slower pharyngeal pumping rate, impaired egg laying, defective motility, and a shortened life span. Here, we generated cell-type specific transgenic worms to determine the cells in which nfi-1 must be expressed to rescue the pharyngeal pumping defect. Expression of nfi-1 from the pharyngeal muscle-specific myo-2 promoter, but not from the F25B3.3 or myo-3 promoters, rescued the pharyngeal pumping defect of nfi-1 worms. Surprisingly, myo-2-driven nfi-1 expression also rescued the shortened lifespan of nfi-1 worms, demonstrating a possible cell-autonomous role of nfi-1 in pharyngeal muscle for both phenotypes. We propose some relationships between the pharyngeal pumping and lifespan phenotypes and potential mechanisms of nfi-1 function.

Conserved Motifs and Prediction of Regulatory Modules inCaenorhabditis elegans

“…This PWM is very similar to the known motif for the TF Pha4, which is known to direct transcription of pharyngeal genes (Gaudet and Mango 2002). In accordance with previous reports that NFI-1 is expressed in muscles (mainly pharynx and head muscles), neurons and intestinal cells (Lazakovitch et al 2005, 2008), our corresponding motif (H01M10.2.1) is also enriched for genes whose GFP-fused promoters are expressed in the pharynx ( P < 3 × 10 −5 ) and body wall muscle ( P < 7 × 10 −3 ).…”

“…Figure 1 shows three different classes of conserved elements that emerge from this analysis. The PWM H01M10.2.1 is likely to represent the binding motif for the TF nuclear factor I-1 (NFI-1) on the basis of several types of evidence: (1) it is highly similar to the documented NFI-1 binding site (Whittle et al 2009) and the vertebrate NF-1 binding site (TRANSFAC AC number: M00056); (2) the gene cluster associated with the H01M10.2.1 matrix is significantly enriched for the known NFI-1 target genes (Whittle et al 2009) ( P < 10 −14 ); (3) the gene cluster associated with the H01M10.2.1 matrix is significantly enriched for genes that are expressed in pharynx ( P < 3 × 10 −5 ) and body wall muscle ( P < 7 × 10 −3 ), which is consistent with observed NFI-1 expression in C. elegans (Lazakovitch et al 2005, 2008); (4) H01M10.2.1 is significantly correlated to NFI-1 ChIP samples ( P < 10 −6 ; t -value ~15.6); and (5) the gene cluster associated with the H01M10.2.1 matrix is significantly enriched for GO terms that are consistent with NFI-1’s function.…”

DNA-binding specificity and in vivo targets of Caenorhabditis elegans nuclear factor I

“…Loss of nfi-1 in C. elegans results in a decreased rate of pharyngeal pumping, impaired egg-laying, altered motility, and a shortened lifespan (6). NFI-1 seems to function autonomously in the pharyngeal muscle with respect to pumping and lifespan (7).…”

Sugar-derived AGEs accelerate pharyngeal pumping rate and increase the lifespan of Caenorhabditis elegans

“…The nematode Caenorhabditis elegans is a model organism very frequently used to study aging. Its pharynx is one of the most essential organs; it is contracted through a coordinated process to perform food intake and distribute it to the animal's digestive tract [11]. Aging has been associated with pumping rate alterations and it has been suggested that the pumping rate can be used as a predictor of lifespan, as prolonged lifespan of the nematode C. elegans has been associated with an increased pumping rate [12].…”