control of transcription by cell size的转录控制细胞的大小.pdf

Control of Transcription by Cell Size 1,2 3 2,3,4 1,2 Chia-Yung Wu , P. Alexander Rolfe , David K. Gifford , Gerald R. Fink * 1 Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 2 Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America, 3 Computer Science and Artificial Intelligence Laboratory, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 4 Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America Abstract Cell size increases significantly with increasing ploidy. Differences in cell size and ploidy are associated with alterations in gene expression, although no direct connection has been made between cell size and transcription. Here we show that ploidy-associated changes in gene expression reflect transcriptional adjustment to a larger cell size, implicating cellular geometry as a key parameter in gene regulation. Using RNA-seq, we identified genes whose expression was altered in a tetraploid as compared with the isogenic haploid. A significant fraction of these genes encode cell surface proteins, suggesting an effect of the enlarged cell size on the differential regulation of these genes. To test this hypothesis, we examined expression of these genes in haploid mutants that also produce enlarged size. Surprisingly, many genes differentially regulated in the tetraploid are identically regulated in the enlarged haploids, and the magnitude of change in gene expression correlates with the degree of s