Histone lysine demethylase 3B regulates autophagy via tran-scriptional regulation of GABARAPL1 in leukemia cell
Macroautophagy (hereafter referred to as autophagy), a highly conserved self-digestion process, is critical for maintaining homeostasis in response to various stresses. The autophagy-related protein family, including the GABARAP (GABA type A receptor-associated protein) and LC3 (microtubule-associated protein 1 light chain 3) subfamilies, is crucial for autophagosome biogenesis. Although the regulation machinery of autophagy in the cytoplasm has been widely studied, its transcriptional and epigenetic regulation mechanisms still require more targeted investigations. Here we identify histone lysine demethylase 3B (KDM3B) as a crucial component of autophagy on a panel of leukemia cell lines, including K562, THP1, and U937, resulting in transcriptional activation of autophagy-related gene GABARAPL1 (GABA type A receptor-associated protein like 1). KDM3B expression promotes autophagosome formation and affects the autophagic flux in leukemia cells under the induction of external stimuli. Notably, RNA-seq and qRT-PCR analysis show that KDM3B knockout inhibited the expression of GABARAPL1. ChIP-qPCR and luciferase assay show that KDM3B associates with GABARAPL1 gene promoter under stimulation and enhances its transcription. Our findings demonstrate that KDM3B is critical for regulating GABARAPL1 gene and influencing the process of autophagy in leukemia cells. These results provide new insight for exploring the relationship between autophagy and KDM3B epigenetic regulation in leukemia.