Kinetic analysis of histone acetylation turnover and Trichostatin A induced hyper- and hypoacetylation in alfalfa

2002 ◽  
Vol 80 (3) ◽  
pp. 279-293 ◽  
Author(s):  
Jakob H Waterborg ◽  
Tamás Kapros
Keyword(s):  
Gene Expression ◽  
Steady State ◽  
Histone Acetylation ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Similar Rate ◽  
Lysine Methylation ◽  
Histone H2a ◽  
Turnover Rates

Dynamic histone acetylation is a characteristic of chromatin transcription. The first estimates for the rate of acetylation turnover of plants are reported, measured in alfalfa cells by pulse, pulse-chase, and steady-state acetylation labeling. Acetylation turnover half-lives of about 0.5 h were observed by all methods used for histones H3, H4, and H2B. This is consistent with the rate at which changes in gene expression occur in plants. Treatment with histone deacetylase inhibitor Trichostatin A (TSA) induced hyperacetylation at a similar rate. Replacement histone variant H3.2, preferentially localized in highly acetylated chromatin, displayed faster acetyl turnover. Histone H2A with a low level of acetylation was not subject to rapid turnover or hyperacetylation. Patterns of acetate labeling revealed fundamental differences between histone H3 versus histones H4 and H2B. In H3, acetylation of all molecules, limited by lysine methylation, had similar rates, independent of the level of lysine acetylation. Acetylation of histones H4 and H2B was seen in only a fraction of all molecules and involved multiacetylation. Acetylation turnover rates increased from mono- to penta- and hexaacetylated forms, respectively. TSA was an effective inhibitor of alfalfa histone deacetylases in vivo and caused a doubling in steady-state acetylation levels by 4–6 h after addition. However, hyperacetylation was transient due to loss of TSA inhibition. TSA-induced overexpression of cellular deacetylase activity produced hypoacetylation by 18 h treatment with enhanced acetate turnover labeling of alfalfa histones. Thus, application of TSA to change gene expression in vivo in plants may have unexpected consequences.

42 EFFECTS OF TRICHOSTATIN A TREATMENT ON GENE EXPRESSION OF CLONED MOUSE 2-CELL AND BLASTOCYST STAGE EMBRYOS

2014 ◽  
Vol 26 (1) ◽  
pp. 135
Author(s):  
S. L. Marjani ◽  
M. G. Carter ◽  
L-Y. Sung ◽  
K. Inoue ◽  
S. Rodriguez-Zas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Cell Types ◽  
Blastocyst Stage ◽  
Cell Stage ◽  
Loess Normalization ◽  
And Control

Trichostatin A (TSA) is a potent inhibitor of histone deacetylases and has been shown to improve cloned embryo pre-implantation and term development. We examined the effects of TSA treatment on cloned mouse embryonic gene expression using microarrays. Cloned mouse embryos were generated using long-term haematopoietic stem cells (LT-HSC) and terminally differentiated granulocytes (Gr-1) as nuclear donors, which have been shown to have significantly different cloning efficiencies (Sung et al. 2006 Nat. Gen. 38, 1323–1328). Late 2-cell and blastocyst stage cloned embryos and control, BDF1 in vivo and IVF embryos (n = 10 from each embryo type and stage, except LT-HSC blastocysts, where n = 5) were snap frozen in liquid nitrogen. Total RNA was isolated from individual embryos and amplified using the TargetAmp 2 round Aminoallyl aRNA amplification kit (Epicentre Biotechnologies, Madison, WI, USA). Amplified RNA from each embryo and a standard reference was labelled with Cy3 or Cy5 and hybridized to the mouse exonic evidence based oligonucleotide (MEEBO) microarray allowing for the interrogation of ~25 000 genes. After Loess normalization, ANOVA with false discovery rate (P < 0.001) was used to identify differentially expressed (DE) genes. A subset of the DE genes was verified by RT-qPCR. These two cell types drastically differed in their potential to give rise to morula/blastocyst stage embryos: LT-HSC: 4.1% v. Gr-1: 38.9%. When treated with 10 nM TSA (Sigma, St. Louis, MO, USA) for 10 h immediately after activation, the morula/blastocyst rate increased to 66.1% for the LT-HSC cloned embryos and to 69.3% for the Gr-1 cloned embryos. At the 2-cell stage, we identified 2172 DE genes between the TSA-treated and untreated LT-HSC embryos. There were 512 DE genes between the Gr-1 and Gr-1 TSA embryos. Interestingly, the cloned embryos were more similar to the in vivo and IVF embryos after TSA treatment at the 2-cell stage, as evidenced by hierarchical clustering and the reduced number of DE genes: LT-HSC v. in vivo = 2622 genes; LT-HSC TSA v. in vivo = 473; Gr-1 v. in vivo = 1448; Gr-1 TSA v. in vivo = 312. By the blastocyst stage, the effect of TSA was considerably less pronounced with 18 and 17 DE genes between the LT-HSC/TSA and Gr-1/TSA embryos, respectively. These data indicate that TSA treatment normalizes 2-cell cloned embryo gene expression, enabling significantly more embryos to develop to the blastocyst stage. Our findings demonstrate that TSA exerted the greatest effect on the LT-HSC embryos, which were the most difficult to reprogram by SCNT.

α2-Adrenoceptor agonist dexmedetomidine protects septic acute kidney injury through increasing BMP-7 and inhibiting HDAC2 and HDAC5

2012 ◽  
Vol 303 (10) ◽  
pp. F1443-F1453 ◽  
Author(s):  
Chung-Hsi Hsing ◽  
Chiou-Feng Lin ◽  
Edmund So ◽  
Ding-Ping Sun ◽  
Tai-Chi Chen ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Histone H3 ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Protective Effects ◽  
Tnf Α

Bone morphogenetic protein (BMP)-7 protects sepsis-induced acute kidney injury (AKI). Dexmedetomidine (DEX), an α2-adrenoceptor (α2-AR) agonist, has anti-inflammatory effects. We investigated the protective effects of DEX on sepsis-induced AKI and the expression of BMP-7 and histone deacetylases (HDACs). In vitro , the effects of DEX or trichostatin A (TSA, an HDAC inhibitor) on TNF-α, monocyte chemotactic protein (MCP-1), BMP-7, and HDAC mRNA expression in LPS-stimulated rat renal tubular epithelial NRK52E cells, was determined using real-time PCR. In vivo, mice were intraperitoneally injected with DEX (25 μg/kg) or saline immediately and 12 h after cecal ligation and puncture (CLP) surgery. Twenty-four hours after CLP, we examined kidney injury and renal TNF-α, MCP-1, BMP-7, and HDAC expression. Survival was monitored for 120 h. LPS increased HDAC2, HDAC5, TNF-α, and MCP-1 expression, but decreased BMP-7 expression in NRK52E cells. DEX treatment decreased the HDAC2, HDAC5, TNF-α, and MCP-1 expression, but increased BMP-7 and acetyl histone H3 expression, whose effects were blocked by yohimbine, an α2-AR antagonist. With DEX treatment, the LPS-induced TNF-α expression and cell death were attenuated in scRNAi-NRK52E but not BMP-7 RNAi-NRK52E cells. In CLP mice, DEX treatment increased survival and attenuated AKI. The expression of HDAC2, HDAC5, TNF-α, and MCP-1 mRNA in the kidneys of CLP mice was increased, but BMP-7 was decreased. However, DEX treatment reduced those changes. DEX reduces sepsis-induced AKI by decreasing TNF-α and MCP-1 and increasing BMP-7, which is associated with decreasing HDAC2 and HDAC5, as well as increasing acetyl histone H3.

scholarly journals The Human Candidate Tumor Suppressor Gene HIC1 Recruits CtBP through a Degenerate GLDLSKK Motif

2002 ◽  
Vol 22 (13) ◽  
pp. 4890-4901 ◽  
Author(s):  
Sophie Deltour ◽  
Sébastien Pinte ◽  
Cateline Guerardel ◽  
Bohdan Wasylyk ◽  
Dominique Leprince
Keyword(s):  
Binding Site ◽  
Transcriptional Repression ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Suppressor Gene ◽  
Close Relative ◽  
Consensus Binding Site ◽  
Candidate Tumor Suppressor Gene

ABSTRACT HIC1 (hypermethylated in cancer) and its close relative HRG22 (HIC1-related gene on chromosome 22) encode transcriptional repressors with five C2H2 zinc fingers and an N-terminal BTB/POZ autonomous transcriptional repression domain that is unable to recruit histone deacetylases (HDACs). Alignment of the HIC1 and HRG22 proteins from various species highlighted a perfectly conserved GLDLSKK/R motif highly related to the consensus CtBP interaction motif (PXDLSXK/R), except for the replacement of the virtually invariant proline by a glycine. HIC1 strongly interacts with mCtBP1 both in vivo and in vitro through this conserved GLDLSKK motif, thus extending the CtBP consensus binding site. The BTB/POZ domain does not interact with mCtBP1, but the dimerization of HIC1 through this domain is required for the interaction with mCtBP1. When tethered to DNA by fusion with the Gal4 DNA-binding domain, the HIC1 central region represses transcription through interactions with CtBP in a trichostatin A-sensitive manner. In conclusion, our results demonstrate that HIC1 mediates transcriptional repression by both HDAC-independent and HDAC-dependent mechanisms and show that CtBP is a HIC1 corepressor that is recruited via a variant binding site.

scholarly journals AGL15 Controls the Embryogenic Reprogramming of Somatic Cells in Arabidopsis through the Histone Acetylation-Mediated Repression of the miRNA Biogenesis Genes

2020 ◽  
Vol 21 (18) ◽  
pp. 6733
Author(s):  
Katarzyna Nowak ◽  
Joanna Morończyk ◽  
Anna Wójcik ◽  
Małgorzata D. Gaj
Keyword(s):  
Histone Acetylation ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Somatic Cells ◽  
Regulatory Function ◽  
Mirna Biogenesis ◽  
Embryogenic Culture ◽  
Cell Transcriptome ◽  
The Impact ◽  
Embryogenic Transition

The embryogenic transition of somatic cells requires an extensive reprogramming of the cell transcriptome. Relevantly, the extensive modulation of the genes that have a regulatory function, in particular the genes encoding the transcription factors (TFs) and miRNAs, have been indicated as controlling somatic embryogenesis (SE) that is induced in vitro in the somatic cells of plants. Identifying the regulatory relationships between the TFs and miRNAs during SE induction is of central importance for understanding the complex regulatory interplay that fine-tunes a cell transcriptome during the embryogenic transition. Hence, here, we analysed the regulatory relationships between AGL15 (AGAMOUS-LIKE 15) TF and miR156 in an embryogenic culture of Arabidopsis. Both AGL15 and miR156 control SE induction and AGL15 has been reported to target the MIR156 genes in planta. The results showed that AGL15 contributes to the regulation of miR156 in an embryogenic culture at two levels that involve the activation of the MIR156 transcription and the containment of the abundance of mature miR156 by repressing the miRNA biogenesis genes DCL1 (DICER-LIKE1), SERRATE and HEN1 (HUA-ENHANCER1). To repress the miRNA biogenesis genes AGL15 seems to co-operate with the TOPLESS co-repressors (TPL and TPR1-4), which are components of the SIN3/HDAC silencing complex. The impact of TSA (trichostatin A), an inhibitor of the HDAC histone deacetylases, on the expression of the miRNA biogenesis genes together with the ChIP results implies that histone deacetylation is involved in the AGL15-mediated repression of miRNA processing. The results indicate that HDAC6 and HDAC19 histone deacetylases might co-operate with AGL15 in silencing the complex that controls the abundance of miR156 during embryogenic induction. This study provides new evidence about the histone acetylation-mediated control of the miRNA pathways during the embryogenic reprogramming of plant somatic cells and the essential role of AGL15 in this regulatory mechanism.

58 HISTONE DEACETYLASES INHIBITOR, SCRIPTAID, IS BENEFICIAL TO THE REPROGRAMMING OF SOMATIC NUCLEI FOLLOWING NUCLEAR TRANSFER

2009 ◽  
Vol 21 (1) ◽  
pp. 129
Author(s):  
J. G. Zhao ◽  
J. W. Ross ◽  
Y. H. Hao ◽  
D. M. Wax ◽  
L. D. Spate ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Histone Deacetylases ◽  
Nuclear Transfer ◽  
Blastocyst Stage ◽  
Untreated Group ◽  
Developmental Competence ◽  
Developmental Potential ◽  
Reconstructed Embryos

Somatic cell nuclear transfer (SCNT) is a promising technology with potential applications in both agriculture and regenerative medicine. The reprogramming of differentiated somatic nuclei into totipotent embryonic state following NT is not efficient and the mechanism is currently unknown. However, accumulating evidence suggests that faulty epigenetic reprogramming is likely to be the major cause of low success rates observed in all mammals produced through SCNT. It has been demonstrated that increased histone acetylation in reconstructed embryos by applying histone deacetylases inhibitor (HDACi) such as trychostatin A (TSA) significantly enhanced the developmental competence in several species in vitro and in vivo. However TSA has been known to be teratogenic. Compared with TSA, Scriptaid is a low toxic but more efficient HDACi (Su GH et al. 2000 Cancer Res. 60, 3137–3142). The objectives of this study were: 1) to investigate and optimize the application Scriptaid to the NT using Landrace fetal fibroblast cells (FFCs) as donor; 2) investigate the effect of increased histone acetylation on the developmental competence of reconstructed embryos from NIH mini inbred FFCs in vitro and in vivo. The reconstructed embryos were treated with Scriptaid at different concentrations (0 nm, 250 nm, 500 nm and 1000 nm) after activation for 14 to 16 h. IVF embryos without treatment were produced as an additional control. Developmental rates to the 2-cell and blastocyst stage were determined. Developmental potential was determined by transferring Day 1 NT zygotes to the oviducts of surrogates on the day of, or one day after, the onset of estrus. Experiments were repeated at least 3 times and data were analyzed with chi-square tests using SAS 6.12 program (SAS institute, Inc., Cary, NC, USA). The percentage blastocyst of cloned embryos using Landrace FFCs as donors treated with 500 nm Scriptaid was the highest and was significantly higher than untreated group (25% v. 11%, P < 0.05). Percent cleaved was not different among four treatment groups. We used 500 nm Scriptaid for 14 to 16 h after activation for all subsequent experiments. Developmental rate to the blastocyst stage was significantly increased in cloned embryos derived from NIH mini inbred FFCs after treating with Scriptaid (21% v. 9%, P < 0.05), while the blastocyst rate in IVF group was 30%. Embryo transfer (ET) results showed that 5/6 (Transferred embryos No. were 190, 109, 154, 174, 152, and 190, respectively) surrogates (83%) became pregnant resulting in 2 healthy piglets from 2 litters (recipients received 190 and 154 embryos, respectively) in the Scriptaid treatment group, while no pregnancies were obtained in the untreated group from 5 ET (Embryos transferred No. are 140, 163, 161, 151 and 151, respectively). These results suggest that 500 nm Scriptaid treatment following activation increase both the in vitro and in vivo development of porcine SCNT embryos from NIH mini inbred FFCs and the hyperacetylation might actually improve reprogramming of the somatic nuclei after NT. Funding from the National Institutes of Health National Center for Research Resources RR018877.

scholarly journals Genome-Wide Relationships between TAF1 and Histone Acetyltransferases in Saccharomyces cerevisiae

2006 ◽  
Vol 26 (7) ◽  
pp. 2791-2802 ◽  
Author(s):  
Melissa Durant ◽  
B. Franklin Pugh
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Histone Acetylation ◽  
Rna Polymerase Ii ◽  
Histone Acetyltransferases ◽  
Histone H4 ◽  
Promoter Regions ◽  
Genome Wide ◽  
Acetylated Histone H4

ABSTRACT Histone acetylation regulates gene expression, yet the functional contributions of the numerous histone acetyltransferases (HATs) to gene expression and their relationships with each other remain largely unexplored. The central role of the putative HAT-containing TAF1 subunit of TFIID in gene expression raises the fundamental question as to what extent, if any, TAF1 contributes to acetylation in vivo and to what extent it is redundant with other HATs. Our findings herein do not support the basic tenet that TAF1 is a major HAT in Saccharomyces cerevisiae, nor do we find that TAF1 is functionally redundant with other HATs, including Gcn5, Elp3, Hat1, Hpa2, Sas3, and Esa1, which is in contrast to previous conclusions regarding Gcn5. Our findings do reveal that of these HATs, only Gcn5 and Esa1 contribute substantially to gene expression genome wide. Interestingly, histone acetylation at promoter regions throughout the genome does not require TAF1 or RNA polymerase II, indicating that most acetylation is likely to precede transcription and not depend upon it. TAF1 function has been linked to Bdf1, which binds TFIID and acetylated histone H4 tails, but no linkage between TAF1 and the H4 HAT Esa1 has been established. Here, we present evidence for such a linkage through Bdf1.

Concurrent opposite effects of trichostatin A, an inhibitor of histone deacetylases, on expression of α-MHC and cardiac tubulins: implication for gain in cardiac muscle contractility

2005 ◽  
Vol 288 (3) ◽  
pp. H1477-H1490 ◽  
Author(s):  
Francesca J. Davis ◽  
Jyothish B Pillai ◽  
Madhu Gupta ◽  
Mahesh P. Gupta
Keyword(s):  
Cardiac Myocytes ◽  
Histone Deacetylases ◽  
Contractile Function ◽  
Trichostatin A ◽  
In Vivo Model ◽  
Ang Ii ◽  
Cardiac Contractile Function ◽  
Noticeable Effect

Histone deacetylases (HDACs) are a family of enzymes that catalyze the removal of acetyl groups from core histones, resulting in change of chromatin structure and gene transcription activity. In the heart, HDACs are targets of hypertrophic signaling, and their nonspecific inhibition by trichostatin A (TSA) attenuates hypertrophy of cultured cardiac myocytes. In this study, we examined the effect of TSA on two major determinants of cardiac contractility: α-myosin heavy chain (MHC) expression and microtubular composition and organization. TSA upregulated the expression of α-MHC in cultured cardiac myocytes, as well as in an in vivo model of hypothyroid rats. Studies designed to delineate mechanisms of α-MHC induction by TSA revealed an obligatory role of early growth response factor-1 on activation of the α-MHC promoter. Concurrently, TSA downregulated the expression of α- and β-tubulins and prevented the induction of tubulins by a hypertrophy agonist, ANG II. The ANG II-mediated increased proportion of α- and β-tubulins associated with polymerized microtubules was also markedly reduced after treatment of cells by TSA. Results obtained from immunofluorescent microscopy indicated that TSA had no noticeable effect on the organization of cardiac microtubules in control cells, whereas it prevented the ANG II-induced dense parallel linear arrays of microtubules to a profile similar to that of controls. Together, these results demonstrate that inhibition of HDACs by TSA regulates the cardiac α-MHC and tubulins in a manner predictive of improved cardiac contractile function. These studies improve our understanding of the role of HDACs on cardiac hypertrophy with implications in development of new therapeutic agents for treatment of cardiac abnormalities.

scholarly journals Multiple Histone Deacetylases and the CREB-binding Protein Regulate Pre-mRNA 3′-End Processing

2006 ◽  
Vol 282 (7) ◽  
pp. 4470-4478 ◽  
Author(s):  
Tadahiro Shimazu ◽  
Sueharu Horinouchi ◽  
Minoru Yoshida
Keyword(s):  
Mass Spectrometry ◽  
Complex Formation ◽  
Nuclear Localization ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Specific Inhibitor ◽  
Creb Binding Protein ◽  
Processing Machinery ◽  
Importin Α

Trichostatin A (TSA), a specific inhibitor of histone deacetylases (HDACs), induces acetylation of various non-histone proteins such as p53 and α-tubulin. We purified several acetylated proteins by the affinity to an anti-acetylated lysine (AcLys) antibody from cells treated with TSA and identified them by mass spectrometry. Here we report on acetylation of CFIm25, a component of mammalian cleavage factor Im (CF Im), and poly(A) polymerase (PAP), a polyadenylating enzyme for the pre-mRNA 3′-end. The residues acetylated in these proteins were mapped onto the regions required for interaction with each other. Whereas CBP acetylated these proteins, HDAC1, HDAC3, HDAC10, SIRT1, and SIRT2 were involved in in vivo deacetylation. Acetylation of the CFIm25 occurred depending on the cleavage factor complex formation. Importantly, the interaction between PAP and CF Im complex was decreased by acetylation. We also demonstrated that acetylation of PAP inhibited the nuclear localization of PAP by inhibiting the binding to the importin α/β complex. These results suggest that CBP and HDACs regulate the 3′-end processing machinery and modulate the localization of PAP through the acetylation and deacetylation cycle.

scholarly journals Unanticipated Repression Function Linked to Erythroid Krüppel-Like Factor

2001 ◽  
Vol 21 (9) ◽  
pp. 3118-3125 ◽  
Author(s):  
Xiaoyong Chen ◽  
James J. Bieker
Keyword(s):  
Gene Expression ◽  
Zinc Finger ◽  
Trichostatin A ◽  
Globin Gene ◽  
Erythroid Cell ◽  
Zinc Finger Domain ◽  
Transcription Activator ◽  
Histone Deacetylase 1 ◽  
Globin Promoter

ABSTRACT The erythroid cell-specific transcription factor erythroid Krüppel-like factor (EKLF) is an important activator of β-globin gene expression. It achieves this by binding to the CACCC element at the β-globin promoter via its zinc finger domain. The coactivators CBP and P300 interact with, acetylate, and enhance its activity, helping to explain its role as a transcription activator. Here we show that EKLF can also interact with the corepressors mSin3A and HDAC1 (histone deacetylase 1) through its zinc finger domain. When linked to a GAL4 DNA binding domain, full-length EKLF or its zinc finger domain alone can repress transcription in vivo. This repressive activity can be relieved by the HDAC inhibitor trichostatin A. Although recruitment of EKLF to a promoter is required to show repression, its zinc finger domain cannot bind directly to DNA and repress transcription simultaneously. In addition, the target promoter configuration is important for enabling EKLF to exhibit any repressive activity. These results suggest that EKLF may function in vivo as a transcription repressor and play a previously unsuspected additional role in regulating erythroid gene expression and differentiation.

scholarly journals Retinoblastoma Protein Disrupts Interactions Required for RNA Polymerase III Transcription

2000 ◽  
Vol 20 (24) ◽  
pp. 9192-9202 ◽  
Author(s):  
Josephine E. Sutcliffe ◽  
Timothy R. P. Brown ◽  
Simon J. Allison ◽  
Pamela H. Scott ◽  
Robert J. White
Keyword(s):  
Rna Polymerase ◽  
Transcriptional Repression ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Rna Polymerase Iii ◽  
Retinoblastoma Protein ◽  
Class Iii ◽  
Negative Effect ◽  
Pol Iii

ABSTRACT The retinoblastoma protein (RB) has been shown to suppress RNA polymerase (Pol) III transcription in vivo (R. J. White, D. Trouche, K. Martin, S. P. Jackson, and T. Kouzarides, Nature 382:88–90, 1996). This regulation involves interaction with TFIIIB, a multisubunit factor that is required for the expression of all Pol III templates (C. G. C. Larminie, C. A. Cairns, R. Mital, K. Martin, T. Kouzarides, S. P. Jackson, and R. J. White, EMBO J. 16:2061–2071, 1997; W.-M. Chu, Z. Wang, R. G. Roeder, and C. W. Schmid, J. Biol. Chem. 272:14755–14761, 1997). However, it has not been established why RB binding to TFIIIB results in transcriptional repression. For several Pol II-transcribed genes, RB has been shown to inhibit expression by recruiting histone deacetylases, which are thought to decrease promoter accessibility. We present evidence that histone deacetylases exert a negative effect on Pol III activity in vivo. However, RB remains able to regulate Pol III transcription in the presence of the histone deacetylase inhibitor trichostatin A. Instead, RB represses by disrupting interactions between TFIIIB and other components of the basal Pol III transcription apparatus. Recruitment of TFIIIB to most class III genes requires its binding to TFIIIC2, but this can be blocked by RB. In addition, RB disrupts the interaction between TFIIIB and Pol III that is essential for transcription. The ability of RB to inhibit these key interactions can explain its action as a potent repressor of class III gene expression.

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