Cell-specific regulation of APOBEC3F by interferons

Human cytidine deaminase APOBEC3F(A3F)has broad anti-viral activity against hepatitis Bvirus and retroviruses including human immunodeficiency virus type 1.However,its regulation in viralnatural target cells such CD4~ T lymphocytes,macrophages,and primary liver cells has not been wellstudied.Here we showed that A3F was up-regulated by interferon(IFN)-α in primary hepatocytes andmultiple liver cell lines as well as macrophages.Although the IFN-α signaling pathway was active in Tlymphoid cells and induction of other IFN stimulated genes such as PKR was detected,A3F and APOBEC3G(A3G)were not induced by IFN-α in these cells.Thus,additional factors other than known IFN-stimulatedgenes also regulated IFN-α-induced A3F expression distinctly.A3F and A3G expression levels in primaryhepatocytes,especially after IFN-α stimulation,were comparable to those in CD4~ T lymphocytes in someindividuals.Significant variations of A3F and A3G expression in primary hepatocytes from various subjectswere observed.Individual variations in A3F and/or A3G regulation and expression might influence the clinicaloutcomes of hepatitis B infection.     

Cell-specific epigenetic regulation of ChM-I gene expression: crosstalk between DNA methylation and histone acetylation

The expression of the chondromodulin-I (ChM-I) gene, a cartilage-specific gene, is regulated by the binding of Sp3 to the core promoter region, which is inhibited by the methylation of CpG in the target genome in the osteogenic lineage, osteosarcoma (OS) cells. The histone tails associated with the hypermethylated promoter region of the ChM-I gene were deacetylated by histone deacetylase 2 (HDAC2) in three ChM-I-negative OS cell lines. Treatment with an HDAC inhibitor induced the binding of Sp3 in one cell line, which became ChM-I-positive. This process was associated with acetylation instead of the dimethylation of histone H3 at lysine 9 (H3-K9) and, surprisingly, the demethylation of the core promoter region. The demethylation was transient, and gradually replaced by methylation after a rapid recovery of histone deacetylaion. These results represent an example of the plasticity of differentiation being regulated by the cell-specific plasticity of epigenetic regulation.