To study the dynamic changes of histone modifications across HSV-1 genome during lytic infection in THP-1 cells. Totally 20 maps of HSV-1 epigenome were generated at 5 different time points after infection, together with their corresponding gene expression profiles.We found that histone modifications were detected on HSV-1 genome soon after infection; all four studied modifications, H3K9me3, H3K27me3, H3K4me3 and H3K27ac, change rapidly along with virus life cycle progression.The transcription repression marks, H3K9me3 and H3K27me3, tended to decrease along with infection process, and the transcription activation mark H3K27ac increased on viral genome, which were aligned with increased expression of viral genes. Moreover, treatment with C646, an inhibitor for H3K27ac transferase p300, inhibited expression of viral genes; and EPZ6438, an inhibitor for H3K27 methyltransferase EZH2, enhanced viral gene expression.
Overall design: To study the distribution of histone modifications on HSV-1 genome during lytic stage, as well as their dynamic changes, we used HSV-1 (1×108 / 10 cm dish) to infect THP-1 cells, and collected samples at 1 hr, 2 hr, 4 hr, 8 hr and 24 hr after infection. The cells were then subjected to RNA-Seq and ChIP-Seq with antibodies recognizing H3K27ac, H3K4me3, H3K9me3 and H3K27me3. Two biological replications were performed for each sequencing and data quality control was done before analysis.
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