Cell identity is maintained by activation of cell-specific gene programs, 
regulated by epigenetic marks, transcription factors and chromatin organization. 
DNA G-quadruplex (G4)-folded regions in cells were reported to be associated 
with either increased or decreased transcriptional activity. By 
G4-ChIP-seq/RNA-seq analysis on liposarcoma cells we confirmed that G4s in 
promoters are invariably associated with high transcription levels in open 
chromatin. Comparing G4 presence, location and transcript levels in liposarcoma 
cells to available data on keratinocytes, we showed that the same promoter 
sequences of the same genes in the two cell lines had different G4-folding 
state: high transcript levels consistently associated with G4-folding. 
Transcription factors AP-1 and SP1, whose binding sites were the most 
significantly represented in G4-folded sequences, coimmunoprecipitated with 
their G4-folded promoters. Thus, G4s and their associated transcription factors 
cooperate to determine cell-specific transcriptional programs, making G4s to 
strongly emerge as new epigenetic regulators of the transcription machinery.