In other word, the promoter-restricted change of histone modifications is one of the governing epigenetic marks in transcriptional regulation. Studies in yeast have demonstrated Figure 6 . Model for GFAP gene activation for induced human astrocytic differentiation. In undifferentiated NTera-2 cells, the presence of the MeCP2 and Sin3A corepressor complex and possibly associated HDAC activity at the GFAP promoter maintain the deacetylated status of chromatin and repress GFAP transcription. Upon cellular differentiation, MeCP2 and Sin3A became dissociated from the GFAP promoter, and the subsequent recruitment of the phosphorylated STAT3 caused a conformational change in the region surrounding the GFAP transcription starting site. This, in turn, facilitated histone H3 acetylation of the promoter resulting from the recruitment of CBP/p300 to exon 1. The combination of chromatin remodeling and promoter conformational changes enabled the recruitment of RNA pol II. doi:10.1371/journal.pone.0022018.g006 that nucleosomes with histone H3K4me3 are associated with actively transcribed genes [75] [76] [77] [78] [79] [80] . Similarly, acetylation of histone H3K9 and H3K14 is critical for the recruitment of transcription factor II D, an initiation step in transcription, and therefore be associated with actively transcribed genes [77, 79, [81] [82] [83] . Histone acetylation is catalyzed by several evolutionarily conserved histone acetyltransferases, including Gcn5/PCAF, TAF1, and CBP/p300 [84] . Genome-wide analysis in human cells confirmed that H3K4me3, H3K9Ac and H3K14Ac are present together at actively transcribed genes [85] . Our ChIP experiments showed that upon GFAP activation after cell differentiation, there were significant increases in active markers of H3K9Ac and H3K14Ac around the STAT3-binding site at the GFAP promoter region. At the same time, H3K4me3 was enriched and overlapped with the peak of RNA polymerase II at the transcription start site. These results support the notion that chromatin remodeling regulated by histone modification is linked to active transcription and provide evidence that the acetylation status of chromatin at the GFAP promoter is likely to be predominant regulator of transcription. Altogether, our study has added a novel regulatory path to GFAP gene expression in addition to DNA methylation.