Transcriptional and chromatin-based partitioning mechanisms uncouple protein scaling from cell size

Biosynthesis scales with cell size such that protein concentrations generally remain constant as cells grow. As an exception, synthesis of the cell-cycle inhibitor Whi5 “sub-scales” with cell size so that its concentration is lower in larger cells to promote cell-cycle entry. Here, we find that tran...

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Bibliographic Details
Published in:Molecular cell 2021-12, Vol.81 (23), p.4861-4875.e7
Main Authors: Swaffer, Matthew P., Kim, Jacob, Chandler-Brown, Devon, Langhinrichs, Maurice, Marinov, Georgi K., Greenleaf, William J., Kundaje, Anshul, Schmoller, Kurt M., Skotheim, Jan M.
Format: Article
Language:English
Subjects:
Cell Cycle
cell size
cell size control
Chromatin - chemistry
Chromatin - metabolism
Computational Biology
gene expression
Gene Expression Regulation, Fungal
Histones - chemistry
Homeostasis
In Situ Hybridization, Fluorescence
Promoter Regions, Genetic
Regression Analysis
Repressor Proteins
RNA, Messenger - metabolism
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins
scaling
Schizosaccharomyces - metabolism
Transcription, Genetic
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Summary:Biosynthesis scales with cell size such that protein concentrations generally remain constant as cells grow. As an exception, synthesis of the cell-cycle inhibitor Whi5 “sub-scales” with cell size so that its concentration is lower in larger cells to promote cell-cycle entry. Here, we find that transcriptional control uncouples Whi5 synthesis from cell size, and we identify histones as the major class of sub-scaling transcripts besides WHI5 by screening for similar genes. Histone synthesis is thereby matched to genome content rather than cell size. Such sub-scaling proteins are challenged by asymmetric cell division because proteins are typically partitioned in proportion to newborn cell volume. To avoid this fate, Whi5 uses chromatin-binding to partition similar protein amounts to each newborn cell regardless of cell size. Disrupting both Whi5 synthesis and chromatin-based partitioning weakens G1 size control. Thus, specific transcriptional and partitioning mechanisms determine protein sub-scaling to control cell size. [Display omitted] •A transcriptional mechanism uncouples Whi5 synthesis from cell size•Histones are the major class of sub-scaling mRNAs in addition to WHI5•Chromatin-based partitioning ensures Whi5 sub-scaling is inherited during division•Disruption of Whi5 sub-scaling weakens G1 size homeostasis Most proteins increase in amount as cell size increases. However, Swaffer et al. show that transcriptional and chromatin-based partitioning mechanisms uncouple Whi5 and histone protein amounts from cell size. This results in Whi5 protein concentration reflecting cell size and delaying cell-cycle entry in smaller cells to control cell size.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2021.10.007