Gene regulation by histone-modifying enzymes under hypoxic conditions: a focus on histone methylation and acetylation

Oxygen, which is necessary for sustaining energy metabolism, is consumed in many biochemical reactions in eukaryotes. When the oxygen supply is insufficient for maintaining multiple homeostatic states at the cellular level, cells are subjected to hypoxic stress. Hypoxia induces adaptive cellular responses mainly through hypoxia-inducible factors (HIFs), which are stabilized and modulate the transcription of various hypoxia-related genes. In addition, many epigenetic regulators, such as DNA methylation, histone modification, histone variants, and adenosine triphosphate-dependent chromatin remodeling factors, play key roles in gene expression. In particular, hypoxic stress influences the activity and gene expression of histone-modifying enzymes, which controls the posttranslational modification of HIFs and histones. This review covers how histone methylation and histone acetylation enzymes modify histone and nonhistone proteins under hypoxic conditions and surveys the impact of epigenetic modifications on gene expression. In addition, future directions in this area are discussed. Hypoxia: revealing effects on gene activation New sequencing technologies are revealing how cells respond to hypoxia, insufficient oxygen, by managing gene activation. In multicellular organisms, gene activation is managed by how tightly a section of DNA is wound around proteins called histones; genes in tightly packed regions are inaccessible and inactive, whereas those in looser regions can be activated. Kyunghwan Kim, Sun-Ju Yi, and co-workers at Chungbuk National University in South Korea have reviewed recent data on how cells regulate gene activity under hypoxic conditions. Advances in sequencing technology have allowed genome-wide studies of how hypoxia affects DNA structure and gene activation, revealing that gene-specific modifications may be more important than genome-wide modifications. Hypoxia is implicated in several diseases, such as cancer and chronic metabolic diseases, and a better understanding of how it affects gene activation may help identify new treatments for hypoxia-related diseases.