scholarly journals Architectural Transcription Factors and the SAGA Complex Function in Parallel Pathways To Activate Transcription

2000 ◽  
Vol 20 (7) ◽  
pp. 2350-2357 ◽  
Author(s):  
Yaxin Yu ◽  
Peter Eriksson ◽  
David J. Stillman
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Rna Polymerase Ii ◽  
Structural Changes ◽  
Critical Role ◽  
Complex Function ◽  
Gene Mutations ◽  
Saga Complex ◽  
Triple Mutant ◽  
Parallel Pathways

ABSTRACT Recent work has shown that transcription of the yeastHO gene involves the sequential recruitment of a series of transcription factors. We have performed a functional analysis ofHO regulation by determining the ability of mutations inSIN1, SIN3, RPD3, andSIN4 negative regulators to permit HOexpression in the absence of certain activators. Mutations in theSIN1 (=SPT2) gene do not affect HOregulation, in contrast to results of other studies using anHO:lacZ reporter, and our data show that the regulatory properties of an HO:lacZ reporter differ from that of the native HO gene. Mutations in SIN3 andRPD3, which encode components of a histone deacetylase complex, show the same pattern of genetic suppression, and this suppression pattern differs from that seen in a sin4mutant. The Sin4 protein is present in two transcriptional regulatory complexes, the RNA polymerase II holoenzyme/mediator and the SAGA histone acetylase complex. Our genetic analysis allows us to conclude that Swi/Snf chromatin remodeling complex has multiple roles inHO activation, and the data suggest that the ability of the SBF transcription factor to bind to the HO promoter may be affected by the acetylation state of the HO promoter. We also demonstrate that the Nhp6 architectural transcription factor, encoded by the redundant NHP6A and NHP6B genes, is required for HO expression. Suppression analysis withsin3, rpd3, and sin4 mutations suggests that Nhp6 and Gcn5 have similar functions. A gcn5 nhp6a nhp6b triple mutant is extremely sick, suggesting that the SAGA complex and the Nhp6 architectural transcription factors function in parallel pathways to activate transcription. We find that disruption ofSIN4 allows this strain to grow at a reasonable rate, indicating a critical role for Sin4 in detecting structural changes in chromatin mediated by Gcn5 and Nhp6. These studies underscore the critical role of chromatin structure in regulating HO gene expression.

scholarly journals Probing Zn2+-binding effects on the zinc-ribbon domain of human general transcription factor TFIIB

2004 ◽  
Vol 378 (2) ◽  
pp. 317-324 ◽  
Author(s):  
Mahua GHOSH ◽  
Laura M. ELSBY ◽  
Tapas K. MAL ◽  
Jane M. GOODING ◽  
Stefan G. E. ROBERTS ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Structural Changes ◽  
Core Promoter ◽  
Critical Role ◽  
General Transcription Factor ◽  
Structural Rigidity ◽  
Zinc Ribbon

The general transcription factor, TFIIB, plays an important role in the assembly of the pre-initiation complex. The N-terminal domain (NTD) of TFIIB contains a zinc-ribbon motif, which is responsible for the recruitment of RNA polymerase II and TFIIF to the core promoter region. Although zinc-ribbon motif structures of eukaryotic and archaeal TFIIBs have been reported previously, the structural role of Zn2+ binding to TFIIB remains to be determined. In the present paper, we report NMR and biochemical studies of human TFIIB NTD, which characterize the structure and dynamics of the TFIIB Zn2+-binding domain in both Zn2+-bound and -free states. The NMR data show that, whereas the backbone fold of NTD is pre-formed in the apo state, Zn2+ binding reduces backbone mobility in the β-turn (Arg28–Gly30), induces enhanced structural rigidity of the charged-cluster domain in the central linker region of TFIIB and appends a positive surface charge within the Zn2+-binding site. V8 protease-sensitivity assays of full-length TFIIB support the Zn2+-dependent structural changes. These structural effects of Zn2+ binding on TFIIB may have a critical role in interactions with its binding partners, such as the Rpb1 subunit of RNA polymerase II.

Interaction of the TFIIB zinc ribbon with RNA polymerase II

2008 ◽  
Vol 36 (4) ◽  
pp. 595-598 ◽  
Author(s):  
Laura M. Elsby ◽  
Stefan G.E. Roberts
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Structural Models ◽  
Initiation Complex ◽  
General Transcription Factors ◽  
Transcription Factor Iib ◽  
General Transcription Factor ◽  
Zinc Ribbon

Transcription by RNA polymerase II requires the assembly of the general transcription factors at the promoter to form a pre-initiation complex. The general transcription factor TF (transcription factor) IIB plays a central role in the assembly of the pre-initiation complex, providing a bridge between promoter-bound TFIID and RNA polymerase II/TFIIF. We have characterized a series of TFIIB mutants in their ability to support transcription and recruit RNA polymerase II to the promoter. Our analyses identify several residues within the TFIIB zinc ribbon that are required for RNA polymerase II assembly. Using the structural models of TFIIB, we describe the interface between the TFIIB zinc ribbon region and RNA polymerase II.

scholarly journals Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate self-renewal of trophoblast stem cells

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Paulina A. Latos ◽  
Angela Goncalves ◽  
David Oxley ◽  
Hisham Mohammed ◽  
Ernest Turro ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Rna Polymerase Ii ◽  
Es Cells ◽  
Embryonic Stem ◽  
Transcriptional Networks ◽  
Self Renewal ◽  
Downstream Target ◽  
Trophoblast Stem

Abstract Esrrb (oestrogen-related receptor beta) is a transcription factor implicated in embryonic stem (ES) cell self-renewal, yet its knockout causes intrauterine lethality due to defects in trophoblast development. Here we show that in trophoblast stem (TS) cells, Esrrb is a downstream target of fibroblast growth factor (Fgf) signalling and is critical to drive TS cell self-renewal. In contrast to its occupancy of pluripotency-associated loci in ES cells, Esrrb sustains the stemness of TS cells by direct binding and regulation of TS cell-specific transcription factors including Elf5 and Eomes. To elucidate the mechanisms whereby Esrrb controls the expression of its targets, we characterized its TS cell-specific interactome using mass spectrometry. Unlike in ES cells, Esrrb interacts in TS cells with the histone demethylase Lsd1 and with the RNA Polymerase II-associated Integrator complex. Our findings provide new insights into both the general and context-dependent wiring of transcription factor networks in stem cells by master transcription factors.

Core promoter elements recognized by transcription factor IIB

2006 ◽  
Vol 34 (6) ◽  
pp. 1051-1053 ◽  
Author(s):  
W. Deng ◽  
S.G.E. Roberts
Keyword(s):  
Transcription Factor ◽  
Rna Polymerase Ii ◽  
Core Promoter ◽  
Critical Role ◽  
Tata Box ◽  
Transcription Factor Iib ◽  
General Transcription Factor ◽  
Recognition Elements ◽  
Recognition Motifs ◽  
Definition Of

The general transcription factor TFIIB (transcription factor IIB) plays a critical role in the assembly of the RNA polymerase II pre-initiation complex. TFIIB can make sequence-specific DNA contacts both upstream and downstream of the TATA box. This has led to the definition of two core promoter BREs (TFIIB-recognition elements), one upstream [BREu (upstream BRE)] and one downstream of TATA box [BREd (downstream BRE)]. TFIIB–BREu and TFIIB–BREd contacts are mediated by two independent DNA-recognition motifs within the core domain of TFIIB. Both the BREu and the BREd modulate the transcriptional potency of a promoter. However, the net effect of the BREs on promoter activity is dependent on the specific blend of elements present within a core promoter.

scholarly journals Genome-wide reduction in chromatin accessibility and unique transcription factor footprints in endothelial cells and fibroblasts in scleroderma skin

2020 ◽  
Author(s):  
Pei-Suen Tsou ◽  
Pamela J. Palisoc ◽  
Mustafa Ali ◽  
Dinesh Khanna ◽  
Amr H Sawalha
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Target Genes ◽  
Critical Role ◽  
Vascular Complications ◽  
Chromatin Accessibility ◽  
Unknown Etiology ◽  
Healthy Controls ◽  
Genome Wide

AbstractSystemic sclerosis (SSc) is a rare autoimmune disease of unknown etiology characterized by widespread fibrosis and vascular complications. We utilized an assay for genome-wide chromatin accessibility to examine the chromatin landscape and transcription factor footprints in both endothelial cells (ECs) and fibroblasts isolated from healthy controls and patients with diffuse cutaneous (dc) SSc. In both cell types, chromatin accessibility was significantly reduced in SSc patients compared to healthy controls. Genes annotated from differentially accessible chromatin regions were enriched in pathways and gene ontologies involved in the nervous system. In addition, our data revealed that chromatin binding of transcription factors SNAI2, ETV2, and ELF1 was significantly increased in dcSSc ECs, while recruitment of RUNX1 and RUNX2 was enriched in dcSSc fibroblasts. Significant elevation of SNAI2 and ETV2 levels in dcSSc ECs, and RUNX2 levels in dcSSc fibroblasts were confirmed. Further analysis of publicly available ETV2-target genes suggests that ETV2 may play a critical role in EC dysfunction in dcSSc. Our data, for the first time, uncovered the chromatin blueprint of dcSSc ECs and fibroblasts, and suggested that neural-related characteristics of SSc ECs and fibroblasts could be a culprit for dysregulated angiogenesis and enhanced fibrosis. Targeting these pathways and the key transcription factors identified might present novel therapeutic approaches for this disease.

Abstract 239: Selective Class I and II Histone Deacetylation Inhibitors Alter Stability of HDAC-Corepressor Complexes

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Hsiao C Wang ◽  
Lillianne G Harris ◽  
James C Chou ◽  
Santhosh Mani ◽  
Donald Menick
Keyword(s):  
Heart Failure ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cardiac Hypertrophy ◽  
Critical Role ◽  
Hdac Inhibitors ◽  
Class I ◽  
Proximal Promoter ◽  
Repressor Complex ◽  
The Stability

Introduction: Alterations in expression and activity of different genes have been implicated in the pathogenesis of heart failure. Our lab has shown that HDAC-repressor complexes play a critical role in the upregulation Sodium Calcium Exchanger ( Ncx1) and HDAC inhibition causes changes that attenuated cardiac remodeling during cardiac hypertrophy and heart failure. Thus, treatment with HDAC inhibitors has been proposed as a potential strategy for treatment of cardiac hypertrophy and heart failure. HDAC inhibitors repress deacetylase activity but we propose that they also affect HDAC confirmation and interaction with other protein factors. We hypothesize that HDAC inhibitors affect the stability of the co-repressor complex with specific transcription factors and that this effect is dependent on the transcription factor. Results: Inhibition of HDACs in adult cardiomyocytes results in the greater stabilization of HDACs with co-repressor molecules that were recruited to the NCX1 promoter through Nkx2.5 transcription factor. HDAC class I specific inhibitor, MS 275 demonstrated stronger association between HDACs and co-repressors while other Class I inhibitors, PD106 and BML 210 failed on showing this phenomenal. The results suggested that class I HDACs inhibitors may affect formations of HDAC-complex via alternated active site interactions other than chelating with zinc binding domain. These results compliment ChIP experiments which also demonstrate the different recruitments of Sin3a at the proximal promoter of NCX1. In vivo analysis on HDAC5 knockout mice reveal that the Sin3a-HDAC1/2 repressor complex is not recruited to the Ncx1 promoter in the absence of HDAC5, indicating not only Class I HDAC but also Class II HDACs play an important role on HDAC-complex formation. Conclusions: This work gives insight into part of the molecular mechanism of how HDAC inhibitors can affect the stability of the HDAC co-repressor complex in cardiac hypertrophy and heart failure. In addition, we demonstrated the Class IIa HDACs are required for the recruitment of the Sin3a/HDAC1/2 co-repressor complex to specific transcription factors on the target promoter.

Analysis of transcription factors binding to the human 7SL RNA gene promoter

1999 ◽  
Vol 77 (5) ◽  
pp. 431-438 ◽  
Author(s):  
Jürgen Müller ◽  
Bernd-Joachim Benecke
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Rna Polymerase Iii ◽  
Gene Promoter ◽  
7Sl Rna ◽  
Polymerase Iii ◽  
Responsive Element

Transcription of the human 7SL RNA gene by RNA polymerase III depends on the concerted action of transcription factors binding to the gene-internal and gene-external parts of its promoter. Here, we investigated which transcription factors interact with the human 7SL RNA gene promoter and which are required for transcription of the human 7SL RNA gene. A-box/B-box elements were previously identified in 5S RNA, tRNA, and virus associated RNA genes and are recognized by transcription factor IIIC (TFIIIC). The gene-internal promoter region of the human 7SL RNA gene shows only limited similarity to those elements. Nevertheless, competition experiments and the use of highly enriched factor preparations demonstrate that TFIIIC is required for human 7SL transcription. The gene-external part of the promoter includes an authentic cAMP-responsive element previously identified in various RNA polymerase II promoters. Here we demonstrate that members of the activating transcription factor/cyclic AMP-responsive element binding protein (ATF/CREB) transcription factor family bind specifically to this element in vitro. However, the human 7SL RNA gene is not regulated by cAMP in vivo. Furthermore, in vitro transcription of the gene does not depend on ATF/CREB transcription factors. It rather appears that a transcription factor with DNA-binding characteristics like ATF/CREB proteins but otherwise different properties is required for human 7SL RNA transcription.Key words: 7SL RNA, ATF, CRE, TFIIIC, RNA polymerase III.

scholarly journals CTCF: the protein, the binding partners, the binding sites and their chromatin loops

2013 ◽  
Vol 368 (1620) ◽  
pp. 20120369 ◽  
Author(s):  
Sjoerd Johannes Bastiaan Holwerda ◽  
Wouter de Laat
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Rna Polymerase Ii ◽  
Binding Sites ◽  
Ctcf Binding ◽  
Chromatin Domain ◽  
Gene Promoters ◽  
Tissue Specific ◽  
Chromatin Loops ◽  
Exact Function

CTCF has it all. The transcription factor binds to tens of thousands of genomic sites, some tissue-specific, others ultra-conserved. It can act as a transcriptional activator, repressor and insulator, and it can pause transcription. CTCF binds at chromatin domain boundaries, at enhancers and gene promoters, and inside gene bodies. It can attract many other transcription factors to chromatin, including tissue-specific transcriptional activators, repressors, cohesin and RNA polymerase II, and it forms chromatin loops. Yet, or perhaps therefore, CTCF's exact function at a given genomic site is unpredictable. It appears to be determined by the associated transcription factors, by the location of the binding site relative to the transcriptional start site of a gene, and by the site's engagement in chromatin loops with other CTCF-binding sites, enhancers or gene promoters. Here, we will discuss genome-wide features of CTCF binding events, as well as locus-specific functions of this remarkable transcription factor.

scholarly journals The Muscle Transcription Factor MyoD Promotes Osteoblast Differentiation by Stimulation of the Osterix Promoter

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3698-3707 ◽  
Author(s):  
Jocelyn Hewitt ◽  
Xiaghuai Lu ◽  
Linda Gilbert ◽  
Mark S. Nanes
Keyword(s):  
Alkaline Phosphatase ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Critical Role ◽  
C2c12 Cells ◽  
Bone Morphogenetic Protein 2 ◽  
Luciferase Reporter ◽  
Upstream Sequence ◽  
Bhlh Transcription Factors ◽  
Stimulation Of

Transcription factors regulate tissue-specific differentiation of pluripotent mesenchyme to osteoblast (OB), myoblast (MB), and other lineages. Osterix (Osx) is an essential transcription factor for bone development because knockout results in lack of a mineralized skeleton. The proximal Osx promoter contains numerous binding sequences for MyoD and 14 repeats of a binding sequence for Myf5. These basic helix-loop-helix (bHLH) transcription factors have a critical role in MB differentiation and muscle development. We tested the hypothesis that bHLH transcription factors also support OB differentiation through regulation of Osx. Transfection of a MyoD expression vector into two primitive mesenchymal cell lines, C3H/10T1/2 and C2C12, stimulated a 1.2-kb Osx promoter-luciferase reporter 70-fold. Myf5 stimulated the Osx promoter 6-fold. Deletion analysis of the promoter revealed that one of three proximal bHLH sites is essential for MyoD activity. The Myf5 repeat conferred 60% of Myf5 activity with additional upstream sequence required for full activity. MyoD bound the active bHLH sequence and its 3′-flanking region, as shown by EMSA and chromatin immunoprecipitation assays. Real-time PCR revealed that primitive C2C12 and C3H/10T1/2 cells, pre-osteoblastic MC3T3 cells, and undifferentiated primary marrow stromal cells express the muscle transcription factors. C2C12 cells, which differentiate to MB spontaneously and form myotubules, were treated with bone morphogenetic protein 2 (BMP-2) to induce OB differentiation. BMP-2 stimulated expression of Osx and the differentiation marker alkaline phosphatase and blocked myotubule development. BMP-2 suppressed the muscle transcription factor myogenin, but expression of MyoD and Myf5 persisted. Silencing of MyoD inhibited BMP-2 stimulation of Osx and blocked the later appearance of bone alkaline phosphatase. MyoD support of Osx transcription contributes to early OB differentiation.

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