In the present study, we developed a new protocol to obtain pure population of astrocyte-like cells from human NTera-2. We revealed a novel role for Sin3A which coupled to MeCP2 and bound to the STAT3-binding site in the GFAP promoter and its occupancy was inversely correlated with de-suppression of GFAP transcription. Sin3A is thought to be devoid of intrinsic DNAbinding capacity, but is able to be recruited by MeCP2 that linked to methylated DNA with HDAC complex. Such formation of corepressor complex by chromatin-bound MeCP2 may lead to local deacetylation of core histones with subsequent transcriptional silencing [52, 61] . Recent reports proposed that another corepressor, N-CoR, controls differentiation of neural stem cells into astrocytes [62] because the complex containing N-CoR, Sin3A and HDAC mediated transcriptional repression [63, 64] . In fact, our phosphoproteomic analysis also confirmed the presence of N-CoR2 in the undifferentiated NTera-2, which declined significantly after cell differentiation (data not shown). These results support transcriptional repression by Sin3A/MeCP2 complex serving as one of the critical mechanisms underlying the inhibition of astrocytic differentiation. It seems that MeCP2 with Sin3A binds to the methylated STAT3-binding site of the GFAP promoter, thus making the site inaccessible to STAT3. Upon cellular differentiation, occupancy by MeCP2 and Sin3A was significantly and specifically diminished at the STAT3-binding site of the GFAP promoter, suggesting a new regulatory path to trigger GFAP activation, in addition to the regulation by STAT3.