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.

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.

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Oxygen is essential to all the aerobic aluminum lotion 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 lolasalinas.com 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.