Acetylation-dependent Multimerization of SAGA Regulates Gene Transcription
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PROVIDER: PRJNA679784 | ENA |
REPOSITORIES: ENA
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Project description:In Saccharomyces cerevisiae, the SAGA complex regulates its own activity by undergoing multimerization. This multimerization is triggered by SAGA autoacetylation at three sites on its Ada3 subunit, allowing recognition of this acetylation by the bromodomain of the Gcn5/Spt7 SAGA subunit. Once multimerized, SAGA is capable of cooperatively acetylating chromatin, and an inability to autoacetylate Ada3 leads to transcriptional and phenotypic defects in a wide range of stress-activated genes. The SAGA multimerization increased significantly in media with Sucorse as the only carbon resource than that with Glucose. In this study, the high-throughput sequence of wild type (WT) strain, Ada3 acetylation mutant (Ada3-3KR), Gcn5 bromodomain mutant (Gcn5m) and Spt7 bromodomain mutant (Spt7m) indicate a new function for Ada3 acetylation, show which genes transcription can be regulated by SAGA multimers.
2021-11-29 | GSE161887 | GEO
Project description:The physiological role of the spliced form of X-box-binding protein 1 (XBP1s), a key transcription factor of the endoplasmic reticulum (ER) stress response, in adipose tissue remains largely unknown. Here we show that overexpression of XBP1s promotes adiponectin multimerization in adipocytes, thereby regulating systemic glucose homeostasis. Ectopic expression of XBP1s in adipocytes improves glucose tolerance and insulin sensitivity in both lean and obese (ob/ob) mice. The beneficial effect of adipocyte XBP1s on glucose homeostasis is associated with elevated serum levels of HMW adiponectin and indeed, is adiponectin dependent. Mechanistically, XBP1s promotes adiponectin multimerization rather than activating its transcription likely through a direct regulation of the expression of several ER-chaperones involved in adiponectin maturation, including Grp78, Pdia6, ERp44 and DsbA-L. Thus, we conclude that XBP1s is an important regulator of adiponectin multimerization, which may lead to a new therapeutic approach for the treatment of type 2 diabetes and hypoadiponectinemia. Epididymal adipose tissue from wild type and XBP1-overexpressing mice was subjected to gene expression profiling.
2013-11-21 | E-GEOD-36031 | biostudies-arrayexpress
Project description:The physiological role of the spliced form of X-box-binding protein 1 (XBP1s), a key transcription factor of the endoplasmic reticulum (ER) stress response, in adipose tissue remains largely unknown. Here we show that overexpression of XBP1s promotes adiponectin multimerization in adipocytes, thereby regulating systemic glucose homeostasis. Ectopic expression of XBP1s in adipocytes improves glucose tolerance and insulin sensitivity in both lean and obese (ob/ob) mice. The beneficial effect of adipocyte XBP1s on glucose homeostasis is associated with elevated serum levels of HMW adiponectin and indeed, is adiponectin dependent. Mechanistically, XBP1s promotes adiponectin multimerization rather than activating its transcription likely through a direct regulation of the expression of several ER-chaperones involved in adiponectin maturation, including Grp78, Pdia6, ERp44 and DsbA-L. Thus, we conclude that XBP1s is an important regulator of adiponectin multimerization, which may lead to a new therapeutic approach for the treatment of type 2 diabetes and hypoadiponectinemia.
2013-11-21 | GSE36031 | GEO
Project description:The SAGA complex is a conserved, multifunctional coactivator that plays broad roles in eukaryotic transcription. Previous studies suggested that Tra1, the largest SAGA component, is required either for SAGA assembly or for recruitment by DNA-bound transcriptional activators. In contrast to S. cerevisiae and mouse, a tra1? mutant is viable in S. pombe, allowing us to test these issues in vivo. We find that, in a tra1? mutant, SAGA assembles and is recruited to some, but not all promoters. Consistent with these findings, Tra1 regulates the expression of only a subset of SAGA-dependent genes. We previously reported that the SAGA subunits Gcn5 and Spt8 have opposing regulatory roles during S. pombe sexual differentiation. We show here that, like Gcn5, Tra1 represses this pathway, although by a distinct mechanism. Thus, our study reveals that Tra1 has specific regulatory roles, rather than global functions, within SAGA.
2011-06-13 | E-MTAB-678 | biostudies-arrayexpress
Project description:SAGA member Ada2 is required for the majority of H3K9 acetylation in C. neoformans. To identify specific genomic loci that exhibit Ada2-dependent H3K9 acetylation, we performed ChIP-Seq against H3K9ac in wildtype and ada2Δ cells.
2012-01-01 | GSE32075 | GEO
Project description:The SAGA (Spt-Ada-Gcn5 acetyltransferase) complex is an evolutionarily conserved, multifunctional co-activator complex, which has a critical role in histone acetylation, gene expression, and various developmental processes in eukaryotes. However, little is known about the composition and function of the SAGA complex in plants. Here, we found that the SAGA complex in Arabidopsis thaliana contains not only conserved subunits and but also four plant-specific subunits, including three homologous subunits, SCS1, SCS2A, and SCS2B (SCS1/2A/2B), and a TAF-like subunit, TAFL. We also found that a series of SAGA subunits are shared in yeast and/or metazoans but are absent in Arabidopsis. Mutations in the unique SAGA subunits SCS1/2A/2B lead to defective phenotypes similar to those caused by mutations in the conserved SAGA subunits HAG1 and ADA2B; these defective phenotypes include delayed juvenile-to-adult phase transition, late flowering, and increased trichome density. SCS1/2A/2B function in the SAGA complex to promote the transcription of development-related genes by facilitating histone H3 acetylation. The results suggest that, compared to SAGA complexes in other eukaryotes, the SAGA complex in plants has evolved unique features that are necessary for normal growth and development.
2021-04-11 | GSE161545 | GEO
Project description:The SAGA (Spt-Ada-Gcn5 acetyltransferase) complex is an evolutionarily conserved, multifunctional co-activator complex, which has a critical role in histone acetylation, gene expression, and various developmental processes in eukaryotes. However, little is known about the composition and function of the SAGA complex in plants. Here, we found that the SAGA complex in Arabidopsis thaliana contains not only conserved subunits and but also four plant-specific subunits, including three homologous subunits, SCS1, SCS2A, and SCS2B (SCS1/2A/2B), and a TAF-like subunit, TAFL. We also found that a series of SAGA subunits are shared in yeast and/or metazoans but are absent in Arabidopsis. Mutations in the unique SAGA subunits SCS1/2A/2B lead to defective phenotypes similar to those caused by mutations in the conserved SAGA subunits HAG1 and ADA2B; these defective phenotypes include delayed juvenile-to-adult phase transition, late flowering, and increased trichome density. SCS1/2A/2B function in the SAGA complex to promote the transcription of development-related genes by facilitating histone H3 acetylation. The results suggest that, compared to SAGA complexes in other eukaryotes, the SAGA complex in plants has evolved unique features that are necessary for normal growth and development.
2021-04-11 | GSE161546 | GEO
Project description:SAGA member Ada2 is required for the majority of H3K9 acetylation in C. neoformans. To identify specific genomic loci that exhibit Ada2-dependent H3K9 acetylation, we performed ChIP-Seq against H3K9ac in wildtype and ada2Δ cells. ChIP-Seq was performed using antibodies for H3K9ac in KN99 wildtype cells and ada2Δ cells. Input and IPed DNA was collected in triplicate from each strain and sequenced on an Illumnina HiSeq 2000 flow cell producing 84 million reads. Due to the lack of quality scores, raw reads are omitted from the submission.
2012-01-01 | E-GEOD-32075 | biostudies-arrayexpress
Project description:Eukaryotic genomes are pervasively transcribed by RNA polymerase II (RNAPII), and transcription of long non-coding RNAs often overlaps with coding gene promoters. This might lead to coding gene repression in a process named Transcription Interference (TI). In Saccharomyces cerevisiae (S. cerevisiae), TI is mainly driven by antisense non-coding transcription and occurs through re-shaping of promoter Nucleosome-Depleted Regions (NDRs). In this study, we developed a genetic screen to identify new players involved in Antisense-Mediated Transcription Interference (AMTI). Among the candidates, we found the HIR histone chaperone complex known to be involved in de novo histone deposition. Using genome-wide approaches, we reveal that HIR-dependent histone deposition represses the promoters of SAGA-dependent genes via antisense non-coding transcription. However, while antisense transcription is enriched at promoters of SAGA-dependent genes, this feature is not sufficient to define the mode of gene regulation. We further show that the balance between HIR-dependent nucleosome incorporation and transcription factor binding at promoters directs transcription into a SAGA- or TFIID-dependent regulation. This study sheds light on a new connection between antisense non-coding transcription and the nature of coding transcription initiation.
2021-06-03 | GSE175991 | GEO
Project description:TFIID and SAGA share a common set of TAFs, regulate chromatin, and deliver TBP to promoters. Here we examine their relationship within the context of the Saccharomyces cerevisiae genome-wide regulatory network. We find that while TFIID and SAGA make overlapping contributions to the expression of all genes, TFIID function predominates at ~90% and SAGA at ~10% of the measurable genome. Strikingly, SAGA-dominated genes are largely stress-induced and TAF-independent, and are down-regulated by the coordinate action of a variety of chromatin, TBP, and RNA polymerase II regulators. In contrast, the TFIID-dominated class is less regulated, but is highly dependent upon TAFs including those shared between TFIID and SAGA. These two distinct modes of transcription regulation might reflect the need to balance inducible stress responses with the steady output of housekeeping genes. Keywords = Taf1 Keywords = Spt3 Keywords = Gcn5
2004-02-26 | E-GEOD-885 | biostudies-arrayexpress