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Transcriptional profiling in C. elegans suggests DNA damage dependent apoptosis as an ancient function of the p53 family.
BMC Genomics. 2008 Jul 15; 9:334.BG

Abstract

BACKGROUND

In contrast to the three mammalian p53 family members, p53, which is generally involved in DNA damage responses, and p63 and p73 which are primarily needed for developmental regulation, cep-1 encodes for the single C. elegans p53-like gene. cep-1 acts as a transcription activator in a primordial p53 pathway that involves CEP-1 activation and the CEP-1 dependent transcriptional induction of the worm BH3 only domain encoding genes egl-1 and ced-13 to induce germ cell apoptosis. EGL-1 and CED-13 proteins inactivate Bcl-2 like CED-9 to trigger CED-4 and CED-3 caspase dependent germ cell apoptosis. To address the function of p53 in global transcriptional regulation we investigate genome-wide transcriptional responses upon DNA damage and cep-1 deficiency.

RESULTS

Examining C. elegans expression profiles using whole genome Affymetrix GeneChip arrays, we found that 83 genes were induced more than two fold upon ionizing radiation (IR). None of these genes, with exception of an ATP ribosylase homolog, encode for known DNA repair genes. Using two independent cep-1 loss of function alleles we did not find genes regulated by cep-1 in the absence of IR. Among the IR-induced genes only three are dependent on cep-1, namely egl-1, ced-13 and a novel C. elegans specific gene. The majority of IR-induced genes appear to be involved in general stress responses, and qRT-PCR experiments indicate that they are mainly expressed in somatic tissues. Interestingly, we reveal an extensive overlap of gene expression changes occurring in response to DNA damage and in response to bacterial infection. Furthermore, many genes induced by IR are also transcriptionally regulated in longevity mutants suggesting that DNA damage and aging induce an overlapping stress response.

CONCLUSION

We performed genome-wide gene expression analyses which indicate that only a surprisingly small number of genes are regulated by CEP-1 and that DNA damage induced apoptosis via the transcriptional induction of BH3 domain proteins is likely to be an ancient DNA damage response function of the p53 family. Interestingly, although the apoptotic response to DNA damage is regulated through the transcriptional activity of CEP-1, other DNA damage responses do not appear to be regulated on the transcriptional level and do not require the p53 like gene cep-1.

Authors+Show Affiliations

Wellcome Trust Centre for Gene Regulation and Expression, School of Life Sciences, The University of Dundee, Dow Street, Dundee DD1 5EH, UK. s.m.greiss@dundee.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18627611

Citation

Greiss, Sebastian, et al. "Transcriptional Profiling in C. Elegans Suggests DNA Damage Dependent Apoptosis as an Ancient Function of the P53 Family." BMC Genomics, vol. 9, 2008, p. 334.
Greiss S, Schumacher B, Grandien K, et al. Transcriptional profiling in C. elegans suggests DNA damage dependent apoptosis as an ancient function of the p53 family. BMC Genomics. 2008;9:334.
Greiss, S., Schumacher, B., Grandien, K., Rothblatt, J., & Gartner, A. (2008). Transcriptional profiling in C. elegans suggests DNA damage dependent apoptosis as an ancient function of the p53 family. BMC Genomics, 9, 334. https://doi.org/10.1186/1471-2164-9-334
Greiss S, et al. Transcriptional Profiling in C. Elegans Suggests DNA Damage Dependent Apoptosis as an Ancient Function of the P53 Family. BMC Genomics. 2008 Jul 15;9:334. PubMed PMID: 18627611.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transcriptional profiling in C. elegans suggests DNA damage dependent apoptosis as an ancient function of the p53 family. AU - Greiss,Sebastian, AU - Schumacher,Björn, AU - Grandien,Kaj, AU - Rothblatt,Jonathan, AU - Gartner,Anton, Y1 - 2008/07/15/ PY - 2008/02/26/received PY - 2008/07/15/accepted PY - 2008/7/17/pubmed PY - 2008/8/21/medline PY - 2008/7/17/entrez SP - 334 EP - 334 JF - BMC genomics JO - BMC Genomics VL - 9 N2 - BACKGROUND: In contrast to the three mammalian p53 family members, p53, which is generally involved in DNA damage responses, and p63 and p73 which are primarily needed for developmental regulation, cep-1 encodes for the single C. elegans p53-like gene. cep-1 acts as a transcription activator in a primordial p53 pathway that involves CEP-1 activation and the CEP-1 dependent transcriptional induction of the worm BH3 only domain encoding genes egl-1 and ced-13 to induce germ cell apoptosis. EGL-1 and CED-13 proteins inactivate Bcl-2 like CED-9 to trigger CED-4 and CED-3 caspase dependent germ cell apoptosis. To address the function of p53 in global transcriptional regulation we investigate genome-wide transcriptional responses upon DNA damage and cep-1 deficiency. RESULTS: Examining C. elegans expression profiles using whole genome Affymetrix GeneChip arrays, we found that 83 genes were induced more than two fold upon ionizing radiation (IR). None of these genes, with exception of an ATP ribosylase homolog, encode for known DNA repair genes. Using two independent cep-1 loss of function alleles we did not find genes regulated by cep-1 in the absence of IR. Among the IR-induced genes only three are dependent on cep-1, namely egl-1, ced-13 and a novel C. elegans specific gene. The majority of IR-induced genes appear to be involved in general stress responses, and qRT-PCR experiments indicate that they are mainly expressed in somatic tissues. Interestingly, we reveal an extensive overlap of gene expression changes occurring in response to DNA damage and in response to bacterial infection. Furthermore, many genes induced by IR are also transcriptionally regulated in longevity mutants suggesting that DNA damage and aging induce an overlapping stress response. CONCLUSION: We performed genome-wide gene expression analyses which indicate that only a surprisingly small number of genes are regulated by CEP-1 and that DNA damage induced apoptosis via the transcriptional induction of BH3 domain proteins is likely to be an ancient DNA damage response function of the p53 family. Interestingly, although the apoptotic response to DNA damage is regulated through the transcriptional activity of CEP-1, other DNA damage responses do not appear to be regulated on the transcriptional level and do not require the p53 like gene cep-1. SN - 1471-2164 UR - https://www.unboundmedicine.com/medline/citation/18627611/Transcriptional_profiling_in_C__elegans_suggests_DNA_damage_dependent_apoptosis_as_an_ancient_function_of_the_p53_family_ L2 - https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-9-334 DB - PRIME DP - Unbound Medicine ER -