The facilitating chromatin transcription (FACT) complex, composed of SSRP1 and Spt16, regulates transcription through chromatin, yet its global role in human cells is not fully defined. This study identifies shared and independent transcriptional targets of SSRP1 and Spt16, including the serum-responsive gene *egr1*, where FACT promotes RNA polymerase II elongation. FACT also associates with casein kinase 2 (CK2), which phosphorylates SSRP1 and modulates its DNA-binding activity, primarily through serine 510. Additionally, SSRP1 is shown to play a novel role in mitosis by regulating microtubule dynamics and spindle organization. Together, these findings reveal multifaceted roles for SSRP1 in transcriptional regulation, cell cycle progression, and growth control.
