Recruitment of the ArgR/Mcm1p repressor is stimulated by the activator Gcn4p: A self-checking activation mechanism

Yoon, Sungpil; Govind, Chhabi K.; Qiu, Hongfang; Kim, Soon-Ja; Dong, Jinsheng; Hinnebusch, Alan G.

doi:10.1073/pnas.0404652101

Cited by 27 publications

(26 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A similar mechanism has been proposed for the regulation of ARG1 transcription in yeast. The expression of ARG1 is induced by the transcriptional activator Gcn4p in response to amino acid starvation and inhibited by the ArgM/ Mcm1p repressor in the presence of arginine (26). Curiously, ArgM/Mcm1 is constitutively recruited to the ARG1 promoter by Gcn4p (26), thus ensuring a balanced, near-quantitative response to the concentration of arginine in the environment.…”

Section: Discussionmentioning

confidence: 99%

GRIP1-associated SET-domain methyltransferase in glucocorticoid receptor target gene expression

Chinenov

Sacta

Cruz

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Transcriptional regulators such as the glucocorticoid receptor (GR) recruit multiple cofactors to activate or repress transcription. Although most cofactors are intrinsically bifunctional, little is known about the molecular mechanisms dictating the specific polarity of regulation. Furthermore, chromatin modifications thought to be confined to silent loci appear in actively transcribed genes suggesting that similar enzymatic activities may mediate constitutive and transient chromatin states. GRIP1, a GR ligand-dependent coregulator of the p160 family can potentiate or inhibit transcription but the molecular contexts and mechanisms that enable GRIP1 corepressor activity are poorly understood. In a yeast 2-hybrid screen with GRIP1 repression domain (RD)-containing fragment, we repeatedly isolated the C-terminal region of a SET domain-containing protein subsequently identified as histone H4 lysine 20 trimethyltransferase, Suv4-20h1. We cloned a full-length Suv4-20h1 and dissected its interaction with GRIP1 in yeast, in vitro, and in mammalian cells. Strict nuclear localization and high salt concentration required for Suv4-20h1 extraction were consistent with its tight association with chromatin. Overexpression of Suv4-20h1 in human U2OS and A549 cells expressing integrated and endogenous GR, respectively, antagonized liganddependent induction of a subset of GR target genes, whereas Suv4-20h1 siRNA-mediated depletion had a reciprocal effect. Inhibition of GR transactivation required both the GRIP1 interacting region of Suv4-20h1 and its catalytic activity. Thus, Suv4-20h1 known exclusively as a factor involved in constitutive heterochromatin maintenance, actively participates in hormone-dependent transcriptional regulation affecting GR target gene expression in a promoter-and cell type-specific manner.

show abstract

Section: Discussionmentioning

confidence: 99%

GRIP1-associated SET-domain methyltransferase in glucocorticoid receptor target gene expression

Chinenov

Sacta

Cruz

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Another possibility is that a Gcn4p-independent mechanism is responsible for the recruitment of SWI/SNF to HIS3, perhaps involving the general transcription factors (27). The recruitment of additional SWI/SNF by Gcn4p at ARG1 might reflect the contribution of other transcription factors not present at HIS3, such as the ArgR complex, which associates with the ARG1 promoter in a Gcn4p-dependent manner (42). In any case, the presence of the SWI/SNF complex on the HIS3 coding region is consistent with a role in gene-wide nucleosome mobilization.…”

Section: Discussionmentioning

confidence: 99%

Activation of Saccharomyces cerevisiae HIS3 Results in Gcn4p-Dependent, SWI/SNF-Dependent Mobilization of Nucleosomes over the Entire Gene

Kim

McLaughlin

Lindstrom

et al. 2006

Molecular and Cellular Biology

View full text Add to dashboard Cite

The effects of transcriptional activation on the chromatin structure of the Saccharomyces cerevisiae HIS3 gene were addressed by mapping the precise positions of nucleosomes in uninduced and induced chromatin. In the absence of the Gcn4p activator, the HIS3 gene is organized into a predominant nucleosomal array. In wild-type chromatin, this array is disrupted, and several alternative overlapping nucleosomal arrays are formed. The disruption of the predominant array also requires the SWI/SNF remodeling machine, indicating that the SWI/SNF complex plays an important role in nucleosome mobilization over the entire HIS3 gene. The Isw1 remodeling complex plays a more subtle role in determining nucleosome positions on HIS3, favoring positions different from those preferred by the SWI/SNF complex. Both the SWI/SNF and Isw1 complexes are constitutively present in HIS3 chromatin, although Isw1 tends to be excluded from the HIS3 promoter. Despite the apparent disorder of HIS3 chromatin generated by the formation of multiple nucleosomal arrays, nucleosome density profiles indicate that some long-range order is always present. We propose that Gcn4p stimulates nucleosome mobilization over the entire HIS3 gene by the SWI/SNF complex. We suggest that the net effect of interplay among remodeling machines at HIS3 is to create a highly dynamic chromatin structure.The central role of chromatin structure in gene regulation is currently the subject of intense interest. Much has been learned about the ATP-dependent chromatin remodeling machines, which use the free energy of ATP hydrolysis to move nucleosomes along DNA and alter nucleosome conformation (31), and the histone-modifying enzymes and their complexes. There is also a great deal of information available concerning changes in chromatin structure occurring at various gene promoters (3,20). Because most of the obvious changes in chromatin structure occur at gene promoters, emphasis has been placed on these events, which are clearly of major importance. However, in our high-resolution studies of the chromatin structure of the CUP1 and HIS3 genes of Saccharomyces cerevisiae, we have obtained evidence pointing to more widespread changes in chromatin structure resulting from induction; these changes involve the entire gene and flanking sequences (9, 29). Our observations indicate that, at least for these genes, chromatin remodeling is not confined to the promoter but occurs on the scale of a chromatin domain.It is now apparent that ATP-dependent chromatin remodeling machines can be grouped into several functional classes (2). One class includes the SWI/SNF and RSC complexes, which are capable of mobilizing nucleosomes and driving a conformational change in the nucleosome to create the remodeled state (24,31). A second class is defined by the ISWI group of complexes, exemplified in budding yeast by the Isw1 and Isw2 complexes, which are capable of mobilizing nucleosomes to create arrays with characteristic spacing but cannot remodel nucleosome structure (19,39). A third class of com...

show abstract

“…The C. albicans ARG genes appear to be independent of the general amino acid control response, in which starvation for any one amino acid activates multiple biosynthetic pathways via the Gcn4p transcription factor in both yeast (reviewed in reference 19) and C. albicans (20). Gcn4p also targets ArgR to ARG promoters as both a positive and negative regulator in yeast (21), but we show that it serves mostly as a repressor of C. albicans ARG loci. Taken together, these data suggest that in response to the oxidative burst generated by macrophages following phagocytosis, C. albicans specifically induces arginine biosynthetic pathway genes to promote filamentous growth within macrophages.…”

mentioning

confidence: 92%

Candida albicans Induces Arginine Biosynthetic Genes in Response to Host-Derived Reactive Oxygen Species

et al. 2013

View full text Add to dashboard Cite

The interaction of Candida albicans with phagocytes of the host's innate immune system is highly dynamic, and its outcome directly impacts the progression of infection. While the switch to hyphal growth within the macrophage is the most obvious physiological response, much of the genetic response reflects nutrient starvation: translational repression and induction of alternative carbon metabolism. Changes in amino acid metabolism are not seen, with the striking exception of arginine biosynthesis, which is upregulated in its entirety during coculture with macrophages. Using single-cell reporters, we showed here that arginine biosynthetic genes are induced specifically in phagocytosed cells. This induction is lower in magnitude than during arginine starvation in vitro and is driven not by an arginine deficiency within the phagocyte but instead by exposure to reactive oxygen species (ROS). Curiously, these genes are induced in a narrow window of sublethal ROS concentrations. C. albicans cells phagocytosed by primary macrophages deficient in the gp91 phox subunit of the phagocyte oxidase do not express the ARG pathway, indicating that the induction is dependent on the phagocyte oxidative burst. C. albicans arg pathway mutants are retarded in germ tube and hypha formation within macrophages but are not notably more sensitive to ROS. We also find that the ARG pathway is regulated not by the general amino acid control response but by transcriptional regulators similar to the Saccharomyces cerevisiae ArgR complex. In summary, phagocytosis induces this single amino acid biosynthetic pathway in an ROS-dependent manner.

show abstract

Recruitment of the ArgR/Mcm1p repressor is stimulated by the activator Gcn4p: A self-checking activation mechanism

Cited by 27 publications

References 26 publications

GRIP1-associated SET-domain methyltransferase in glucocorticoid receptor target gene expression

GRIP1-associated SET-domain methyltransferase in glucocorticoid receptor target gene expression

Activation of Saccharomyces cerevisiae HIS3 Results in Gcn4p-Dependent, SWI/SNF-Dependent Mobilization of Nucleosomes over the Entire Gene

Candida albicans Induces Arginine Biosynthetic Genes in Response to Host-Derived Reactive Oxygen Species

Contact Info

Product

Resources

About