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A CBP/p300 homolog specifies multiple differentiation pathways in Caenorhabditis elegans
Abstract:
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.
Insights
The Caenorhabditis elegans gene cbp-1 is essential for somatic cell differentiation. Its inhibition leads to developmental arrest, highlighting CBP-1
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Mammalian p300 and CBP are transcriptional cofactors with histone acetyltransferase activity, crucial for cell growth and differentiation.
- Inactivation of CBP/p300 by adenovirus E1A is linked to oncogenic transformation and inhibited differentiation.
- A related gene in Caenorhabditis elegans, cbp-1, is investigated for its role in early development.
Purpose of the Study:
- To investigate the function of the Caenorhabditis elegans cbp-1 gene during early embryogenesis.
- To determine the role of CBP-1 in specifying differentiation pathways in C. elegans.
- To explore the relationship between CBP-1 and histone deacetylase in regulating somatic differentiation.
Main Methods:
- Analysis of cbp-1 gene function in Caenorhabditis elegans embryos.
- Observation of developmental phenotypes resulting from cbp-1 inhibition.
- Comparative analysis with C. elegans genes related to mammalian histone deacetylases.
Main Results:
- Inhibition of cbp-1 causes developmental arrest in C. elegans embryos without morphogenesis but with increased cell numbers.
- Mesodermal, endodermal, and hypodermal cell differentiation are absent in cbp-1 inhibited embryos.
- Neuronal differentiation is observed in all cbp-1 inhibited embryos, suggesting CBP-1 promotes non-neuronal somatic differentiation.
Conclusions:
- CBP-1 plays a critical role in promoting all non-neuronal somatic differentiation pathways in C. elegans embryos.
- C. elegans histone deacetylase-related genes appear to repress somatic differentiation.
- A model is proposed where CBP-1 activates transcription and differentiation by antagonizing histone deacetylase repression.