ASF1A regulates H4Y72 phosphorylation and promotes autophagy in colon cancer cells via a kinase activity. Issue 1 (4th December 2019) - Qiu, Fei
Abstract: Colon cancer is one of the most malignant cancers. Histone modification is closely related to tumour development. Our study explored the functions of anti-silencing function 1A (ASF1A) on H4 Y72ph in colon cancer cells. Colon cancer cell lines and clinical specimens were obtained and/or transfected with full length ASF1A or interference mRNA to mimic or silence of ASF1A expression. Immunoprecipitation and GST pull down was used to target targeting ASF1A or H4 Y72ph . Cells were transfected with H4 WT - or H4 Y72F -expressing. An in vitro kinase activity assay was set to determine whether ASF1A could phosphorylate H4. The severity of autophagy was measured by detecting number of autophagosomes, number of EGFP-LC3, LC3-II/I, percentage of degradation and expression of autophagy associated gene (ATG). ASF1A positively regulated H4 Y72ph ; Immunoprecipitation assay and GST pull down results showed that ASF1A interacted directly with H4. In addition, ASF1A silence inhibited autophagosomes number, EGFP-LC3 number, LC3-II/I, percentage of degradation and ATG expression. Moreover, H4 Y72F impaired the promoting autophagy effects of ASF1A. The ASF1A-H4 Y72ph axis promoted colon cancer autophagy via transcriptional regulation of ATG genes. ASF1A regulated H4 Y72ph and promotes autophagy in colon cancer cells via a kinase activity through regulation of ATG.