A CBP/p300 homolog specifies multiple differentiation pathways in Caenorhabditis elegans.
Mammalian p300 and CBP are related transcriptional cofactors that possess histone acetyltransferase activity. Inactivation of CBP/p300 is critical for adenovirus E1A to induce oncogenic transformation and to inhibit differentiation, suggesting that these proteins are likely to play a role in cell growth and differentiation. Here we show that a Caenorhabditis elegans gene closely related to CBP/p300, referred to as cbp-1, is required during early embryogenesis to specify several major differentiation pathways. Inhibition of cbp-1 expression causes developmental arrest of C. elegans embryos with no evidence of body morphogenesis but with nearly twice the normal complement of embryonic cells. Mesodermal, endodermal, and hypodermal cells appear to be completely absent in most embryos, however, all of the embryos exhibit evidence of neuronal differentiation. Our analysis of this phenotype suggests a critical role for CBP-1 in promoting all non-neuronal pathways of somatic differentiation in the C. elegans embryo. In contrast, we show that C. elegans genes related to components of a conserved mammalian histone deacetylase, appear to have a role in repressing somatic differentiation. Our findings suggest a model in which CBP-1 may activate transcription and differentiation in C. elegans by directly or indirectly antagonizing a repressive effect of histone deacetylase.
Shi
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Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115 USA.
Mello
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C
D000123:Acetyltransferases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D004707:Endoderm / Q000502:physiology; D017238:Genes, Helminth / Q000235:genetics / Q000502:physiology*; D015801:Helminth Proteins / Q000235:genetics* / Q000502:physiology; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000378:metabolism; D008648:Mesoderm / Q000502:physiology; D008969:Molecular Sequence Data; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015801:Helminth Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C020723:citrate-binding transport protein; D000123:Acetyltransferases; C111709:CBP-1 protein, C elegans; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases