Whole genome profiling of short-term hypoxia induced genes and identification of HIF-1 binding sites provide insights into HIF-1 function in Caenorhabditis elegans.
PLoS One
; 19(5): e0295094, 2024.
Article
em En
| MEDLINE
| ID: mdl-38743782
ABSTRACT
Oxygen is essential to all the aerobic organisms. However, during normal development, disease and homeostasis, organisms are often challenged by hypoxia (oxygen deprivation). Hypoxia-inducible transcription factors (HIFs) are master regulators of hypoxia response and are evolutionarily conserved in metazoans. The homolog of HIF in the genetic model organism C. elegans is HIF-1. In this study, we aimed to understand short-term hypoxia response to identify HIF-1 downstream genes and identify HIF-1 direct targets in C. elegans. The central research questions were (1) which genes are differentially expressed in response to short-term hypoxia? (2) Which of these changes in gene expression are dependent upon HIF-1 function? (3) Are any of these hif-1-dependent genes essential to survival in hypoxia? (4) Which genes are the direct targets of HIF-1? We combine whole genome gene expression analyses and chromatin immunoprecipitation sequencing (ChIP-seq) experiments to address these questions. In agreement with other published studies, we report that HIF-1-dependent hypoxia-responsive genes are involved in metabolism and stress response. Some HIF-1-dependent hypoxia-responsive genes like efk-1 and phy-2 dramatically impact survival in hypoxic conditions. Genes regulated by HIF-1 and hypoxia overlap with genes responsive to hydrogen sulfide, also overlap with genes regulated by DAF-16. The genomic regions that co-immunoprecipitate with HIF-1 are strongly enriched for genes involved in stress response. Further, some of these potential HIF-1 direct targets are differentially expressed under short-term hypoxia or are differentially regulated by mutations that enhance HIF-1 activity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Caenorhabditis elegans
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Proteínas de Caenorhabditis elegans
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Fator 1 Induzível por Hipóxia
Limite:
Animals
Idioma:
En
Revista:
PLoS ONE (Online)
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PLoS One
/
PLos ONE
Assunto da revista:
CIENCIA
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MEDICINA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos