Table 4

Selected transcription factors significantly represented in genes in CHE and DE_SigUp with examples of functions

TFTFBS enriched inErythroid-related functions
CREB CHE, DE_SigUp Key mediator of myeloid differentiation and proliferation 
AP2/ERF CHE Transcriptional repressor, induces erythroid differentiation in K562 and HEL cells30  
E2F CHE, DE_SigUp E2F plays critical roles in cell cycle progression by regulating the expression of genes involved in nucleotide synthesis, DNA replication, and cell cycle control as demonstrated in mouse models.38  E2F has recently been shown to form a complex with GATA1, FOG1, and retinoblastoma protein (pRb), thus stalling cell proliferation and steering erythroid precursors toward terminal differentiation.39  
NFY(A) (CAAT-binding protein) CHE, DE_SigUp Binds human β-globin promoter in K562 cells, stabilizing a complex formed with MZF1 and GATA2. Appears important in maintaining a chromatin conformation favorable to β-globin transcription.40  
SP1 CHE, DE_SigUp Ubiquitously expressed. Acts synergistically with FOXM1, GATA1,27  OCT, and AP2, which are also highlighted in DiRE analysis of DE_SigUp. 
TATA/TBP DE_SigUp TBP is essential for long-range activation of β-globin transcription in response to the HS2 enhancer located 10 kb from the promoter.41  
TFTFBS enriched inErythroid-related functions
CREB CHE, DE_SigUp Key mediator of myeloid differentiation and proliferation 
AP2/ERF CHE Transcriptional repressor, induces erythroid differentiation in K562 and HEL cells30  
E2F CHE, DE_SigUp E2F plays critical roles in cell cycle progression by regulating the expression of genes involved in nucleotide synthesis, DNA replication, and cell cycle control as demonstrated in mouse models.38  E2F has recently been shown to form a complex with GATA1, FOG1, and retinoblastoma protein (pRb), thus stalling cell proliferation and steering erythroid precursors toward terminal differentiation.39  
NFY(A) (CAAT-binding protein) CHE, DE_SigUp Binds human β-globin promoter in K562 cells, stabilizing a complex formed with MZF1 and GATA2. Appears important in maintaining a chromatin conformation favorable to β-globin transcription.40  
SP1 CHE, DE_SigUp Ubiquitously expressed. Acts synergistically with FOXM1, GATA1,27  OCT, and AP2, which are also highlighted in DiRE analysis of DE_SigUp. 
TATA/TBP DE_SigUp TBP is essential for long-range activation of β-globin transcription in response to the HS2 enhancer located 10 kb from the promoter.41  

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