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Swaffer, M.P.* ; Kim, J.* ; Chandler-Brown, D.* ; Langhinrichs, M.* ; Marinov, G.K.* ; Greenleaf, W.J.* ; Kundaje, A.* ; Schmoller, K.M. ; Skotheim, J.M.*

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

Mol. Cell 81, 4861-4875.e7 (2021)
Postprint DOI PMC
Open Access Green
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cell Cycle ; Cell Size ; Cell Size Control ; Gene Expression ; Scaling; Gene-expression; Budding-yeast; Saccharomyces-cerevisiae; Protein Localization; G1/s Transcription; Cycle Control; Rna-synthesis; Copy Number; Growth; Identification
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 1097-2765
e-ISSN 1097-4164
Journal Molecular Cell
Quellenangaben Volume: 81, Issue: 23, Pages: 4861-4875.e7 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Functional Epigenetics (IFE)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-554400-001
Grants Stanford MPTP T32 training grant
Human Frontier Science Program
EMBO Long-Term Postdoctoral Fellowship
Simons Foundation Fellowship of the Life Sciences Research Foundation
HHMI-Simons
NIH
DOI 10.1016/j.molcel.2021.10.007
WOS ID WOS:000727246500001
Scopus ID 85119918698
PubMed ID 34731644
Erfassungsdatum 2021-12-02
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