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

Mol Cell. 2021 Dec 2;81(23):4861-4875.e7. doi: 10.1016/j.molcel.2021.10.007. Epub 2021 Nov 2.


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.

Keywords: cell cycle; cell size; cell size control; gene expression; scaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Chromatin / chemistry*
  • Chromatin / metabolism
  • Computational Biology
  • Gene Expression Regulation, Fungal*
  • Histones / chemistry
  • Homeostasis
  • In Situ Hybridization, Fluorescence
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • Regression Analysis
  • Repressor Proteins
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces / metabolism*
  • Transcription, Genetic*


  • Chromatin
  • Histones
  • RNA, Messenger
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Whi5 protein, S cerevisiae