Regulatory mechanism of ABCB1 transcriptional repression by HDAC5 in rat hepatocytes under hypoxic environment

In BRL cells, HDAC5 may be recruited by SP1 to form a complex, reducing free HDAC5, increasing H3K9ac at the <i>ABCB1B</i> promoter, and activating ABCB1 transcription. In the BRL hypoxia model, disruption of the SP1-HDAC5 complex increased free HDAC5, lowered H3K9ac at the <i>ABCB1B</i> promoter, and suppressed ABCB1 transcription. These results suggest that HDAC inhibitors enhance ABCB1 expression in hypoxic environments, indicating that combining HDAC inhibitors with therapeutic agents could mitigate reduced drug efficacy and adverse effects caused by ABCB1 suppression.