Premium
MAD1 and c‐MYC regulate UBF and rDNA transcription during granulocyte differentiation
Author(s) -
Poortinga Gretchen,
Hannan Katherine M,
Snelling Hayley,
Walkley Carl R,
Jenkins Anna,
Sharkey Kerith,
Wall Meaghan,
Brandenburger Yves,
Palatsides Manuela,
Pearson Richard B,
McArthur Grant A,
Hannan Ross D
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600335
Subject(s) - biology , ribosome biogenesis , transcription factor , transcription (linguistics) , rna polymerase i , microbiology and biotechnology , cell cycle , promoter , cell growth , general transcription factor , ribosome , cell , rna polymerase , gene expression , genetics , rna , gene , linguistics , philosophy
The regulation of cell mass (cell growth) is often tightly coupled to the cell division cycle (cell proliferation). Ribosome biogenesis and the control of rDNA transcription through RNA polymerase I are known to be critical determinants of cell growth. Here we show that granulocytic cells deficient in the c‐MYC antagonist MAD1 display increased cell volume, rDNA transcription and protein synthesis. MAD1 repressed and c‐MYC activated rDNA transcription in nuclear run‐on assays. Repression of rDNA transcription by MAD1 was associated with its ability to interact directly with the promoter of upstream binding factor (UBF), an rDNA regulatory factor. Conversely, c‐MYC activated transcription from the UBF promoter. Using siRNA, UBF was shown to be required for c‐MYC‐induced rDNA transcription. These data demonstrate that MAD1 and c‐MYC reciprocally regulate rDNA transcription, providing a mechanism for coordination of ribosome biogenesis and cell growth under conditions of sustained growth inhibition such as granulocyte differentiation.