Incoherent feed-forward regulatory logic underpinning glucocorticoid receptor action.

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.

authors

Chen SH,Masuno K,Cooper SB,Yamamoto KR

doi

10.1073/pnas.1216108110

subject

Has Abstract

pub_date

2013-01-29 00:00:00

pages

1964-9

issue

5

eissn

0027-8424

issn

1091-6490

pii

1216108110

journal_volume

110

pub_type

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