Forkhead transcription factors, Fkh1p and Fkh2p, collaborate with Mcm1p tocontrol transcription required for M-phase

Background: The 'CLB2 cluster' in Saccharomyces cerevisiae consists of appr oximately 33 genes whose transcription peaks in late G2/early M phase of th e cell cycle. Many of these genes are required for execution of the mitotic program and then for cytokinesis, The transcription factor SFF (SWI5 facto r) is thought to regulate a program of mitotic transcription in conjunction with the general transcription factor Mcm1p. The identity of SFF has yet t o be determined; hence further understanding of the mechanisms that regulat e entry to M phase at the transcriptional level requires characterization o f SFF at the molecular level. Results: We have purified the biochemical activity corresponding to SFF and identified it as the forkhead transcription factor Fkh2p. Fkh2p assembles into ternary complexes with Mcm1p on both the SW/5 and CLB2 cell-cycle-regu lated upstream activating sequence (UAS) elements in vitro, and in an Mcm1p -dependent manner in vivo. Another closely related forkhead protein, Fkh1p, is also recruited to the CLB2 promoter in vivo. We show that both FKH1 and FKH2 play essential roles in the activation of the CLB2 cluster genes duri ng G2-M and in establishing their transcriptional periodicity. Hence, Fkh1p and Fkhp2 show the properties expected of SFF, both in vitro and in vivo. Conclusions: Forkhead transcription factors have redundant roles in the con trol of CLB2 cluster genes during the G2-M period of the cell cycle, in col laboration with Mcm1p. (C) 2000 Elsevier Science Ltd. All rights reserved.