EEL-1, a Hect E3 ubiquitin ligase, controls asymmetry and persistence of the SKN-1 transcription factor in the early C. elegans embryo.
During early divisions of the C. elegans embryo, many maternally supplied determinants accumulate asymmetrically, and this asymmetry is crucial for proper cell fate specification. SKN-1, a transcription factor whose message is maternally supplied to the embryo, specifies the mesendodermal cell fate. In the 2-cell embryo, SKN-1 is expressed at a higher level in the posterior cell. This asymmetry becomes more pronounced at the 4-cell stage, when SKN-1 is high in the posterior cell's daughters and low in the daughters of the anterior blastomere. To date, the direct mechanisms that control SKN-1 distribution remain unknown. In this report, we identify eel-1, which encodes a putative Hect E3 ubiquitin ligase that shares several domains of similarity to the mammalian E3 ligase Mule. EEL-1 binds SKN-1 and appears to target SKN-1 for degradation. EEL-1 has two functions in regulating SKN-1 during early embryogenesis. First, eel-1 promotes the spatial asymmetry of SKN-1 accumulation at the 2- and 4-cell stages. Second, eel-1 acts in all cells to downregulate SKN-1 from the 12- to the 28-cell stage. Although loss of eel-1 alone causes a reduction in SKN-1 asymmetry at the 2-cell stage, the function of eel-1 in both the spatial and temporal regulation of SKN-1 is redundant with the activities of other genes. These data strongly suggest that multiple, functionally redundant pathways cooperate to ensure precise control of SKN-1 asymmetry and persistence in the early embryo.
Page
Barbara D
BD
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. bdpage@gmail.com
Diede
Scott J
SJ
Tenlen
Jennifer R
JR
Ferguson
Edwin L
EL
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D002875:Chromosomes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian; D049452:Green Fluorescent Proteins; D008954:Models, Biological; D009154:Mutation; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; C073702:skn-1 protein, C elegans; C521393:EEL-1 protein, C elegans; D044767:Ubiquitin-Protein Ligases