Size-independent mRNA synthesis and chromatin-based partitioning mechanisms generate and maintain constant amounts of protein per cell

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 a transcriptional control uncouples Whi5 synthesis from cell size and, screening for similar genes, identify histones as the major class of sub-scaling transcripts besides WHI5. 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 new-born cell volume. To avoid this fate, Whi5 uses chromatin-binding to partition similar protein amounts to each new-born cell regardless of cell size. Finally, disrupting both Whi5 synthesis and chromatin-based partitioning compromises G1 size control. Thus, specific transcriptional and partitioning mechanisms determine protein sub-scaling to control cell size.