Snf1--a Histone Kinase That Works in Concert with the Histone Acetyltransferase Gcn5 to Regulate Transcription

Science ◽  
2001 ◽  
Vol 293 (5532) ◽  
pp. 1142-1146 ◽  
Author(s):  
W.-S. Lo
Keyword(s):  
Histone Acetyltransferase ◽  
Histone Acetyltransferase Gcn5 ◽  
Histone Kinase

scholarly journals A unique GCN5 histone acetyltransferase complex controls erythrocyte invasion and virulence in the malaria parasite Plasmodium falciparum

2021 ◽  
Author(s):  
Jun Miao ◽  
Chengqi Wang ◽  
Amuza Lucky ◽  
Xiaoying Liang ◽  
Hui Min ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Transcription Factor ◽  
Histone Acetyltransferase ◽  
Cellular Processes ◽  
H3k4 Trimethylation ◽  
Erythrocyte Invasion ◽  
Histone Acetyltransferase Gcn5 ◽  
Parasitic Protist ◽  
Activator Complex

AbstractThe histone acetyltransferase GCN5-associated SAGA complex is evolutionarily conserved from yeast to human and functions as a general transcription co-activator in global gene regulation. In this study, we identified a divergent GCN5 complex in Plasmodium falciparum, which contains two plant homeodomain (PHD) proteins (PfPHD1 and PfPHD2) and a plant apetela2 (AP2)-domain transcription factor (PfAP2-LT). To dissect the functions of the PfGCN5 complex, we generated parasites with the bromodomain deletion in PfGCN5 and the PHD domain deletion in PfPHD1. The two deletion mutants closely phenocopied each other, exhibiting significantly reduced merozoite invasion of erythrocytes and elevated sexual conversion. These domain deletions caused dramatic decreases not only in histone H3K9 acetylation but also in H3K4 trimethylation, indicating synergistic crosstalk between the two euchromatin marks. Domain deletion in either PfGCN5 or PfPHD1 profoundly disturbed the global transcription pattern, causing altered expression of more than 60% of the genes. At the schizont stage, these domain deletions were linked to specific downregulation of merozoite genes involved in erythrocyte invasion, many of which harbor the DNA-binding motifs for AP2-LT and/or AP2-I, suggesting targeted recruitment of the PfGCN5 complex to the invasion genes by these specific transcription factors. Conversely, at the ring stage, PfGCN5 or PfPHD1 domain deletions disrupted the mutually exclusive expression pattern of the entire var gene family, which encodes the virulent factor PfEMP1. Correlation analysis between the chromatin state and alteration of gene expression demonstrated that up- and down-regulated genes in these mutants are highly correlated with the silenct and active chromatin states in the wild-type parasite, respectively. Collectively, the PfGCN5 complex represents a novel HAT complex with a unique subunit composition including the AP2 transcription factor, which signifies a new paradigm for targeting the co-activator complex to regulate general and parasite-specific cellular processes in this low-branching parasitic protist.Author SummaryEpigenetic regulation of gene expression plays essential roles in orchestrating the general and parasite-specific cellular pathways in the malaria parasite Plasmodium falciparum. Using tandem affinity purification and proteomic characterization, we identified a divergent transcription co-activator – the histone acetyltransferase GCN5-associated complex in P. falciparum, which contains nine core components, including two PHD domain proteins (PfPHD1 and PfPHD2) and a plant apetela2-domain transcription factor. To understand the functions of the PfGCN5 complex, we performed gene disruption in two subunits of this complex, PfGCN5 and PfPHD1. We found that the two deletion mutants displayed very similar growth phenotypes, including significantly reduced merozoite invasion rates and elevated sexual conversion. These two mutants were associated with dramatic decreases in histone H3K9 acetylation and H3K4 trimethylation, which led to global changes in chromatin states and gene expression. Genes significantly affected by the PfGCN5 and PfPHD1 gene disruption include those participating in parasite-specific pathways such as invasion, virulence, and sexual development. In conclusion, this study presents a new model of the PfGCN5 complex for targeting the co-activator complex to regulate general and parasite-specific cellular processes in this low-branching parasitic protist.

scholarly journals Cryptococcus neoformans Histone Acetyltransferase Gcn5 Regulates Fungal Adaptation to the Host

2010 ◽  
Vol 9 (8) ◽  
pp. 1193-1202 ◽  
Author(s):  
Teresa R. O'Meara ◽  
Christie Hay ◽  
Michael S. Price ◽  
Steve Giles ◽  
J. Andrew Alspaugh
Keyword(s):  
Cryptococcus Neoformans ◽  
Chromatin Remodeling ◽  
Histone Acetyltransferase ◽  
Transcriptional Responses ◽  
Content Type ◽  
Human Host ◽  
Cellular Effects ◽  
Histone Acetyltransferase Gcn5 ◽  
Increased Sensitivity ◽  
Opportunistic Human Pathogen

ABSTRACT Cryptococcus neoformans is an environmental fungus and an opportunistic human pathogen. Previous studies have demonstrated major alterations in its transcriptional profile as this microorganism enters the hostile environment of the human host. To assess the role of chromatin remodeling in host-induced transcriptional responses, we identified the C. neoformans Gcn5 histone acetyltransferase and demonstrated its function by complementation studies of Saccharomyces cerevisiae. The C. neoformans gcn5Δ mutant strain has defects in high-temperature growth and capsule attachment to the cell surface, in addition to increased sensitivity to FK506 and oxidative stress. Treatment of wild-type cells with the histone acetyltransferase inhibitor garcinol mimics cellular effects of the gcn5 Δ mutation. Gcn5 regulates the expression of many genes that are important in responding to the specific environmental conditions encountered by C. neoformans inside the host. Accordingly, the gcn5 Δ mutant is avirulent in animal models of cryptococcosis. Our study demonstrates the importance of chromatin remodeling by the conserved histone acetyltransferase Gcn5 in regulating the expression of specific genes that allow C. neoformans to respond appropriately to the human host.

scholarly journals PFKFB4 negatively regulated the expression of histone acetyltransferase GCN5 to mediate the tumorigenesis of thyroid cancer

2020 ◽  
Vol 62 (2) ◽  
pp. 129-138
Author(s):  
Huanquan Lu ◽  
Siyuan Chen ◽  
Zhijian You ◽  
Chuping Xie ◽  
Shichuan Huang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Histone Acetyltransferase ◽  
Histone Acetyltransferase Gcn5

scholarly journals And-1 is required for the stability of histone acetyltransferase Gcn5

Oncogene ◽  
2011 ◽  
Vol 31 (5) ◽  
pp. 643-652 ◽  
Author(s):  
Y Li ◽  
A N Jaramillo-Lambert ◽  
Y Yang ◽  
R Williams ◽  
N H Lee ◽  
...  
Keyword(s):  
Histone Acetyltransferase ◽  
Histone Acetyltransferase Gcn5 ◽  
The Stability

scholarly journals Kinetic Mechanism of the Histone Acetyltransferase GCN5 from Yeast

2000 ◽  
Vol 275 (29) ◽  
pp. 22048-22055 ◽  
Author(s):  
Kirk G. Tanner ◽  
Michael R. Langer ◽  
Youngjoo Kim ◽  
John M. Denu
Keyword(s):  
Histone Acetyltransferase ◽  
Kinetic Mechanism ◽  
Histone Acetyltransferase Gcn5
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