We have previously reported Foxk1 as an important transcription factor in the myogenic progenitors. SWI-independent-3 (Sin3) has been identified as a Foxk1 binding candidate using a yeast two-hybrid screen. In the present study, we have identified the Foxk1 N-terminal (1-40) region as the Sin3 interacting domain (SID), and the PAH2 of Sin3 as the Foxk1 binding domain utilizing yeast two-hybrid and GST pull-down assays. Further studies revealed that knockdown of Sin3a or Sin3b results in cell cycle arrest and upregulation of cell cycle inhibitor genes. In summary, our present studies have shown that Foxk1 interacts with Sin3 through the SID and that Sin3 has an important role in the regulation of cell cycle kinetics of the MPC population. The results of these studies continue to define and assemble the networks that regulate the MPCs and muscle regeneration.