Abstract:
:The complexity and specificity of metazoan transcription are determined by combinatorial control of the composition and activity of regulatory complexes. To investigate the basis of this specificity, we focused on the glucocorticoid receptor (GR), a single regulatory factor that integrates multiple signals to give rise to many distinct patterns of expression. We measured the expression of a set of genes, each directly GR-regulated, but by different mechanisms in two cell lines. We varied ligand (dose, chemistry, and duration of treatment), GR (expression level and functionality), and a non-GR regulatory factor that commonly interacts with GR. Our study revealed distinct expression patterns within this set of genes, but all could be modeled by an incoherent feed-forward regulatory logic. Cellular signals, operating on GR and other factors within regulatory complexes, may define and modulate the kinetics and strength of the activating or inhibitory paths of the regulatory logic. Thus, characterizing systems behavior by perturbing single or multiple signals can reveal general principles of regulation, providing an approach to the dissection and deconvolution of combinatorial control.
journal_name
Proc Natl Acad Sci U S Aauthors
Chen SH,Masuno K,Cooper SB,Yamamoto KRdoi
10.1073/pnas.1216108110subject
Has Abstractpub_date
2013-01-29 00:00:00pages
1964-9issue
5eissn
0027-8424issn
1091-6490pii
1216108110journal_volume
110pub_type
杂志文章abstract::The switch from fetal to adult hemoglobin expression is regulated in many mammalian species by a developmental clock-like mechanism and determined by the gestational age of the fetus. Prolonging fetal globin gene expression is of considerable interest for therapeutic potential in diseases caused by abnormal beta-globi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.22.8540
更新日期:1988-11-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.80.24.7437
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pub_type: 杂志文章
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.072557199
更新日期:2002-04-02 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.23.13448
更新日期:1998-11-10 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2015-03-31 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1998-06-09 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2012-10-16 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2011-02-08 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2004-04-06 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1108220109
更新日期:2012-04-03 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2006-12-05 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:1976-11-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:1988-01-01 00:00:00
abstract::Cells are exposed to changes in extracellular stimulus concentration that vary as a function of rate. However, how cells integrate information conveyed from stimulation rate along with concentration remains poorly understood. Here, we examined how varying the rate of stress application alters budding yeast mitogen-act...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2021-01-12 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2009-03-03 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.2.648
更新日期:1977-02-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:1995-12-19 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.20.6461
更新日期:1984-10-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2020-09-22 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.67.2.757
更新日期:1970-10-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2003-06-24 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0506880102
更新日期:2005-11-15 00:00:00
abstract::Rap phosphatases are a recently discovered family of protein aspartate phosphatases that dephosphorylate the Spo0F--P intermediate of the phosphorelay, thus preventing sporulation of Bacillus subtilis. They are regulators induced by physiological processes that are antithetical to sporulation. The RapA phosphatase is ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.4.1549
更新日期:1996-02-20 00:00:00
abstract::The human papillomavirus E7 protein is phosphorylated at the two serines in positions 31/32, which are part of a consensus sequence for casein kinase II (CKII). In this study, we have investigated the effect of CKII phosphorylation site mutations, all of which lead to unphosphorylated E7 proteins. The replacement of t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.12.5187
更新日期:1991-06-15 00:00:00