Our previous study revealed that PDCD2 plays a role in erythroid differentiation (unpublished data).To get a further view, RNA-seq analyses of control and PDCD2-KD TF-1 cells were conducted, and 574 differentially-expressed genes (DEGs) were identified including 221 up-regulated genes and 353 down-regulated genes.Up-regulated genes in PDCD2-KD were mainly enriched in DNA binding and chromatin organization, whereas down-regulated genes in PDCD2-KD were enriched in immune response and regulation of cell proliferation.Furthermore, the gene set (31 genes) derived from up-regulated genes in the PDCD2-KD group significantly enriched in positional gene sets CHR6P22 of chromosome 6 (FDR < 25%).These genes mainly belong to histone family, including HIST1H1B,HIST1H3F, and HIST 1H4D, and participate in systemic lupus erythematosus pathway.In addition,increased histone3 acetylation level was observed at several cis-regulation elements at β-globin locus.Taken together, our data imply that PDCD2 regulates erythroid differentiation possibly by affecting the function of histone proteins.