Hypoxia promotes histone H3K9 lactylation to enhance LAMC2 transcription in esophageal squamous cell carcinoma
Hypoxia promotes tumorigenesis and lactate accumulation in esophageal squamous cell carcinoma (ESCC). Lactate can induce histone lysine lactylation (Kla, a recently-identified histone marks) to regulate transcription. However, the functional consequence of histone Kla under hypoxia in ESCC remains to be explored. Here, we reveal that hypoxia facilitates histone H3K9la to enhance LAMC2 transcription for proliferation of ESCC. We found that global level of Kla was elevated under hypoxia, and thus identified the landscape of histone Kla in ESCC by quantitative proteomics. Furthermore, we show a significant increase of H3K9la level induced by hypoxia. Next, MNseq ChIP-seq and RNA-seq analysis suggest that H3K9la is enriched at the promoter of cell junction genes. Finally, we demonstrate that the histone H3K9la facilitates the expression of LAMC2 for ESCC invasion by in vivo and in vitro experiments. Briefly, our study reveal a vital role of histone Kla triggered by hypoxia in cancer. Overall design: To investigate the function of hypoxia  in KYSE30 cells, we cultured KYSE30 cells in hypoxia or normoxia environment.To investigate the function of LAMC2  in KYSE30 cells,we established LAMC2 overexpressed KYSE30 cell lines. MNseq Chromatin immunoprecipitation (MNseq ChIP-seq) for histone 3 lysine 9 lactylation in KYSE30cells cultured in hypoxia or normoxia environment