Fig 6. Timing transcriptional activation by relaxing interference from the cell cycle.

(A) Proposed model in which the N/C input feeds into the MBT through its influence on the cell cycle. During the syncytial cycles, increasing N/C contributes to the increasing duration of the cell cycle. Interphase lengthening allows more time for gene expression and for completion of longer transcripts. Onset of expression of genes such as tribbles triggers further cell cycle slowing by engaging a switch-like shutoff of cyclin/Cdk1 by inhibitory phosphorylation that is enhanced by feedback through the expression of additional inhibitors of cell cycle progression. This switch in cyclin/Cdk1 activity, in conjunction with dynamic transcriptional programs, transforms the regulatory architecture of the embryo. (B) The duration of interphase of pre-MBT cell cycles (red) with the time available to extend transcripts indicated (blue). The eclipse times for H2B and rRNA are given on the right. As expected, their transcription begins when the window of transcription exceeds the eclipse time. (C) Expression efficiency of primary transcripts of four different lengths as function of cell cycle progression. The larger transcription units have a later and more abrupt onset of productive expression. Note that this displays the earliest times that transcripts can be expressed, but their onset can be delayed by additional promoter-specific regulation. Except for cycle 14, which is simply set at 100%, the time-averaged percent expression was obtained by subtracting mitotic time, lag time, and eclipse time from the cell cycle length to determine the time during which complete transcripts can be produced and this is divided by total cell cycle time. This time average estimates a maximal relative efficiency of expression. Numerical data for panels B and C can be found in the file S1 Data.xlsx. MBT, mid-blastula transition; N/C, ratio of nuclei to cytoplasm.