Abstract
Author SummaryAsymmetric cell division is a universal mechanism for generating differentiated cells. The progeny of such divisions can often display differential cell cycle regulation. This study addresses how differential regulation of gene expression in the progeny of a single division can alter cell cycle control. In budding yeast, asymmetric cell division yields a bigger ‘mother’ cell and a smaller ‘daughter’ cell. Regulation of gene expression is also asymmetric because two transcription factors, Ace2 and Ash1, are specifically localized to the daughter. Cell size has long been proposed as important for the regulation of the cell cycle in yeast. Our work shows that Ace2 and Ash1 regulate size control in daughter cells: daughters ‘interpret’ their size as smaller, making size control more stringent and delaying cell cycle commitment relative to mother cells of the same size. This asymmetric interpretation of cell size is associated with differential regulation of the G1 cyclin CLN3 by Ace2 and Ash1, at least in part via direct binding of these factors to the CLN3 promoter. CLN3 is the most upstream regulator of Start, the initiation point of the yeast cell cycle, and differential regulation of CLN3 accounts for most or all asymmetric regulation of Start in budding yeast mother and daughter cells.
Highlights
At the Start transition in G1, budding yeast cells integrate internal and external cues into an all-or-none commitment to a new round of cell division [1,2]
Our work shows that Ace2 and Ash1 regulate size control in daughter cells: daughters ‘interpret’ their size as smaller, making size control more stringent and delaying cell cycle commitment relative to mother cells of the same size
We provide evidence that Ash1 binds to the CLN3 promoter and that this binding is at least in part mediated by Ash1 consensus-binding sites that are different from the Daughter Delay Elements (DDE)
Summary
At the Start transition in G1, budding yeast cells integrate internal and external cues into an all-or-none commitment to a new round of cell division [1,2]. The regulation of G1 phase is composed of two independent modules separated by the nuclear exit of the transcriptional repressor Whi5 [5]: a cell size sensing module, which extends G1 in small cells to allow additional growth before Start [5], and a subsequent size-independent module [5,6]. The fast and coherent transition between the two modules likely coincides with commitment to the cell cycle and is driven by transcriptional positive feedback [7]. Cln initiates inactivation of Whi5 [13,14] and expression of SBF/MBF dependent genes, including the G1 cyclins CLN1 and CLN2 [9,11,12,15,16]. Subsequent positive feedback of Cln and Cln on SBF/MBF dependent transcription ensures fast and coherent commitment to the cell cycle [7]
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