The concerted action of multiple genes in a time-dependent manner controls complex cellular phenotypes, yet the temporal regulation of gene expressions is restricted on a single-gene level, which limits our ability to control higher-order gene networks and understand the consequences of multiplex genetic perturbations. Here we developed a system for temporal regulation of multiple genes. This s...

A double-negative feedback loop formed by the morning genes CIRCADIAN CLOCK ASSOCIATED1 (CCA1)/LATE ELONGATED HYPOCOTYL (LHY) and the evening gene TIMING OF CAB EXPRESSION1 (TOC1) contributes to regulation of the circadian clock in Arabidopsis. A 24-h circadian cycle starts with the peak expression of CCA1 at dawn. Although CCA1 is targeted by multiple transcriptional repressors, including PSEU...

We show that the intracellular concentration of transcriptional activator proteins is regulated by the proteasome-mediated protein degradation pathway. The rate of degradation of activators by proteasomes correlates with activation domain potency in vivo. Mutations either in the activation domain residues involved in target protein interaction or in the DNA-binding domain residues essential for...

Transcriptional activators play a central role in gene regulation by stimulating the assembly of the transcriptional machinery at a promoter in a signal-responsive manner. Because of the significant role that misregulated or malfunctioning transcriptional activators play in human disease, there has been a strong effort towards the identification of molecules that inhibit the ability of an activ...

Tomato Cf genes encode membrane-bound proteins with extracellular leucine-rich repeats, and confer resistance to the fungal tomato pathogen Cladosporium fulvum, and a hypersensitive response (HR) to C. fulvum-derived race-specific elicitors. Several Cf genes, including Cf-4 and Cf-9, are members of the highly homologous Hcr9 (homologues of C. fulvumresistance gene Cf-9) gene family. Hcr9s evolv...

Transcription of eukaryotic genes is a complex process requiring the action of a myriad of proteins. Central to the process is the large multi-subunit enzyme RNA polymerase II (Pol II), which contains 12 subunits (Lewin, 1997). In spite of its complexity, Pol II requires a series of general transcription factors (GTFs) to recognize, bind, and clear the core promoter of each gene. These GTFs are...

Abstract Stochastic fluctuations at the transcriptional level contribute to isogenic cell-to-cell heterogeneity in mammalian cell populations. However, we still have no clear understanding of repercussions this heterogeneity, given lack tools independently control mean expression and variability a gene. Here, engineer synthetic circuit modulate transgenes endogenous human genes. The circuit, Tu...

The CREB regulated transcription co-activators (CRTCs) regulate many biological processes by integrating and converting environmental inputs into transcriptional responses. Although the mechanisms by which CRTCs sense cellular signals are characterized, little is known regarding how CRTCs contribute to the regulation of cAMP inducible genes. Here we show that these dynamic regulators, unlike ot...

The nuclear orphan receptor CAR is active in the absence of ligand with the unique capability to be further regulated by activators. A number of these activators, including phenobarbital, do not directly bind to the receptor. Considered a xenobiotic sensing receptor, CAR transcriptionally modifies the expression of genes involved in the metabolism and elimination of xenobiotics and steroids in ...