Transcription Regulation

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Gianni Carraro - One of the best experts on this subject based on the ideXlab platform.

  • high mobility group protein mediated Transcription requires dna damage marker γ h2ax
    Cell Research, 2015
    Co-Authors: Indrabahadur Singh, Nihan Ozturk, Julio Cordero, Aditi Mehta, Diya Hasan, Claudia Cosentino, Carlos Sebastian, Mario Looso, Marcus Kruger, Gianni Carraro
    Abstract:

    The eukaryotic genome is organized into chromatins, the physiological template for DNA-dependent processes including replication, recombination, repair, and Transcription. Chromatin-mediated Transcription Regulation involves DNA methylation, chromatin remodeling, and histone modifications. However, chromatin also contains non-histone chromatin-associated proteins, of which the high-mobility group (HMG) proteins are the most abundant. Although it is known that HMG proteins induce structural changes of chromatin, the processes underlying Transcription Regulation by HMG proteins are poorly understood. Here we decipher the molecular mechanism of Transcription Regulation mediated by the HMG AT-hook 2 protein (HMGA2). We combined proteomic, ChIP-seq, and transcriptome data to show that HMGA2-induced Transcription requires phosphorylation of the histone variant H2AX at S139 (H2AXS139ph; γ-H2AX) mediated by the protein kinase ataxia telangiectasia mutated (ATM). Furthermore, we demonstrate the biological relevance of this mechanism within the context of TGFβ1 signaling. The interplay between HMGA2, ATM, and H2AX is a novel mechanism of Transcription initiation. Our results link H2AXS139ph to Transcription, assigning a new function for this DNA damage marker. Controlled chromatin opening during Transcription may involve intermediates with DNA breaks that may require mechanisms that ensure the integrity of the genome.

Indrabahadur Singh - One of the best experts on this subject based on the ideXlab platform.

  • high mobility group protein mediated Transcription requires dna damage marker γ h2ax
    Cell Research, 2015
    Co-Authors: Indrabahadur Singh, Nihan Ozturk, Julio Cordero, Aditi Mehta, Diya Hasan, Claudia Cosentino, Carlos Sebastian, Mario Looso, Marcus Kruger, Gianni Carraro
    Abstract:

    The eukaryotic genome is organized into chromatins, the physiological template for DNA-dependent processes including replication, recombination, repair, and Transcription. Chromatin-mediated Transcription Regulation involves DNA methylation, chromatin remodeling, and histone modifications. However, chromatin also contains non-histone chromatin-associated proteins, of which the high-mobility group (HMG) proteins are the most abundant. Although it is known that HMG proteins induce structural changes of chromatin, the processes underlying Transcription Regulation by HMG proteins are poorly understood. Here we decipher the molecular mechanism of Transcription Regulation mediated by the HMG AT-hook 2 protein (HMGA2). We combined proteomic, ChIP-seq, and transcriptome data to show that HMGA2-induced Transcription requires phosphorylation of the histone variant H2AX at S139 (H2AXS139ph; γ-H2AX) mediated by the protein kinase ataxia telangiectasia mutated (ATM). Furthermore, we demonstrate the biological relevance of this mechanism within the context of TGFβ1 signaling. The interplay between HMGA2, ATM, and H2AX is a novel mechanism of Transcription initiation. Our results link H2AXS139ph to Transcription, assigning a new function for this DNA damage marker. Controlled chromatin opening during Transcription may involve intermediates with DNA breaks that may require mechanisms that ensure the integrity of the genome.

Konstantin Severinov - One of the best experts on this subject based on the ideXlab platform.

  • controller protein of restriction modification system kpn2i affects Transcription of its gene by acting as a Transcription elongation roadblock
    Nucleic Acids Research, 2018
    Co-Authors: Evgeny Klimuk, Maxim Nagornykh, E A Bogdanova, Marko Djordjevic, Andjela Rodic, Sofia Medvedeva, Olga Pavlova, Konstantin Severinov
    Abstract:

    C-proteins control restriction-modification (R-M) systems' genes Transcription to ensure sufficient levels of restriction endonuclease to allow protection from foreign DNA while avoiding its modification by excess methyltransferase. Here, we characterize Transcription Regulation in C-protein dependent R-M system Kpn2I. The Kpn2I restriction endonuclease gene is transcribed from a constitutive, weak promoter, which, atypically, is C-protein independent. Kpn2I C-protein (C.Kpn2I) binds upstream of the strong methyltransferase gene promoter and inhibits it, likely by preventing the interaction of the RNA polymerase sigma subunit with the -35 consensus element. Diminished Transcription from the methyltransferase promoter increases Transcription from overlapping divergent C-protein gene promoters. All known C-proteins affect Transcription initiation from R-M genes promoters. Uniquely, the C.Kpn2I binding site is located within the coding region of its gene. C.Kpn2I acts as a roadblock stalling elongating RNA polymerase and decreasing production of full-length C.Kpn2I mRNA. Mathematical modeling shows that this unusual mode of Regulation leads to the same dynamics of accumulation of R-M gene transcripts as observed in systems where C-proteins act at Transcription initiation stage only. Bioinformatics analyses suggest that Transcription Regulation through binding of C.Kpn2I-like proteins within the coding regions of their genes may be widespread.

  • Transcription Regulation of restriction modification system esp1396i
    Nucleic Acids Research, 2009
    Co-Authors: E A Bogdanova, M V Zakharova, Tomasz Heyduk, Geoff Kneale, Simon Streeter, James E Taylor, Konstantin Severinov
    Abstract:

    Restriction-modification (R-M) system Ecl18kI is representative of R-M systems whose coordinated Transcription is achieved through a separate DNA-binding domain of the methyltransferase. M.Ecl18kI recognizes an operator sequence located in the noncoding region that separates the divergently transcribed R and M genes. Here we show that, contrary to previous predictions, the two ecl18kI promoters are not divergent, but actually face one another. The binding of M.Ecl18kI to its operator prevents RNA polymerase (RNAP) binding to the M promoter by steric exclusion, but has no direct effect on RNAP interaction with the R promoter. The start point for R Transcription is located outside of the intergenic region, opposite the initiation codon of the M gene. Regulated Transcription of the potentially toxic ecl18kI R gene is accomplished (i) at the stage of promoter complex formation, through direct competition from complexes formed at the M promoter, and (ii) at the stage of promoter clearance, since R promoter-bound RNAP escapes the promoter more slowly than RNAP bound to the M promoter.

  • Transcription Regulation of the type ii restriction modification system ahdi
    Nucleic Acids Research, 2008
    Co-Authors: E A Bogdanova, Marko Djordjevic, Ioanna Papapanagiotou, Tomasz Heyduk, Geoff Kneale, Konstantin Severinov
    Abstract:

    The Restriction-modification system AhdI contains two convergent Transcription units, one with genes encoding methyltransferase subunits M and S and another with genes encoding the controller (C) protein and the restriction endonuclease (R). We show that AhdI Transcription is controlled by two independent regulatory loops that are well-optimized to ensure successful establishment in a naive bacterial host. Transcription from the strong MS promoter is attenuated by methylation of an AhdI site overlapping the -10 element of the promoter. Transcription from the weak CR promoter is regulated by the C protein interaction with two DNA-binding sites. The interaction with the promoter-distal high-affinity site activates Transcription, while interaction with the weaker promoter-proximal site represses it. Because of high levels of cooperativity, both C protein-binding sites are always occupied in the absence of RNA polymerase, raising a question how activated Transcription is achieved. We develop a mathematical model that is in quantitative agreement with the experiment and indicates that RNA polymerase outcompetes C protein from the promoter-proximal-binding site. Such an unusual mechanism leads to a very inefficient activation of the R gene Transcription, which presumably helps control the level of the endonuclease in the cell.

  • Transcription antitermination by translation initiation factor if1
    Journal of Bacteriology, 2007
    Co-Authors: Sangita Phadtare, Tatyana V Pestova, Teymur Kazakov, Mikhail Bubunenko, Donald L Court, Konstantin Severinov
    Abstract:

    Bacterial translation initiation factor IF1 is an S1 domain protein that belongs to the oligomer binding (OB) fold proteins. Cold shock domain (CSD)-containing proteins such as CspA (the major cold shock protein of Escherichia coli) and its homologues also belong to the OB fold protein family. The striking structural similarity between IF1 and CspA homologues suggests a functional overlap between these proteins. Certain members of the CspA family of cold shock proteins act as nucleic acid chaperones: they melt secondary structures in nucleic acids and act as Transcription antiterminators. This activity may help the cell to acclimatize to low temperatures, since cold-induced stabilization of secondary structures in nascent RNA can impede Transcription elongation. Here we show that the E. coli translation initiation factor, IF1, also has RNA chaperone activity and acts as a Transcription antiterminator in vivo and in vitro. We further show that the RNA chaperone activity of IF1, although critical for Transcription antitermination, is not essential for its role in supporting cell growth, which presumably functions in translation. The results thus indicate that IF1 may participate in Transcription Regulation and that cross talk and/or functional overlap may exist between the Csp family proteins, known to be involved in Transcription Regulation at cold shock, and S1 domain proteins, known to function in translation.

  • Transcription Regulation of the EcoRV restriction-modification system.
    Nucleic acids research, 2005
    Co-Authors: Ekaterina Semenova, Maxim Nagornykh, M V Zakharova, Tomasz Heyduk, Leonid Minakhin, Ekaterina A. Bogdanova, Anatoliy Vasilov, Alexander S. Solonin, Konstantin Severinov
    Abstract:

    When a plasmid containing restriction–modification (R–M) genes enters a nao¨ve host, unmodified host DNA can be destroyed by restriction endonuclease. Therefore, expression of R–M genes must be regulated to ensure that enough methyltransferase is produced and that host DNA is methylated before the endonuclease synthesis begins. In several R–M systems, specialized Control (C) proteins coordinate expression of the R and the M genes. C proteins bind to DNA sequences called C-boxes and activate expression of their cognate R genes and inhibit the M gene expression, however the mechanisms remain undefined. Here, we studied the Regulation of gene expression in the C protein-dependent EcoRV system. We map the divergent EcoRV M and R gene promoters and we define the site of C protein-binding that is sufficient for activation of the EcoRV R Transcription.

Yongfeng Shang - One of the best experts on this subject based on the ideXlab platform.

  • utx promotes hormonally responsive breast carcinogenesis through feed forward Transcription Regulation with estrogen receptor
    Oncogene, 2017
    Co-Authors: Y. Zhang, Zhaolong Chen, Bosen Xu, Xia Yi, Wenmei Li, Yongfeng Shang, Zihan Zhang, Lin He, Jinbo Yang
    Abstract:

    UTX promotes hormonally responsive breast carcinogenesis through feed-forward Transcription Regulation with estrogen receptor

  • the molecular mechanism governing the oncogenic potential of sox2 in breast cancer
    Journal of Biological Chemistry, 2008
    Co-Authors: Yupeng Chen, Lei Shi, Lirong Zhang, Jing Liang, Luyang Sun, Xiaohan Yang, Yan Wang, Yu Zhang, Yongfeng Shang
    Abstract:

    SOX genes encode a family of high-mobility group Transcription factors that play critical roles in organogenesis. The functional specificity of different SOX proteins and the tissue specificity of a particular SOX factor are largely determined by the differential partnership of SOX Transcription factors with other Transcription regulators, many of which have not yet been discovered. Virtually all members of the SOX family have been found to be deregulated in a wide variety of tumors. However, little is known about the cellular and molecular behaviors involved in the oncogenic potential of SOX proteins. Using cell culture experiments, tissue analysis, molecular profiling, and animal studies, we report here that SOX2 promotes cell proliferation and tumorigenesis by facilitating the G(1)/S transition and through its Transcription Regulation of the CCND1 gene in breast cancer cells. In addition, we identified beta-catenin as the Transcription partner for SOX2 and demonstrated that SOX2 and beta-catenin act in synergy in the Transcription Regulation of CCND1 in breast cancer cells. Our experiments not only determined a role for SOX2 in mammary tumorigenesis but also revealed another activity of the multifunctional protein, beta-catenin.

Dylan J Taatjes - One of the best experts on this subject based on the ideXlab platform.

  • single molecule assay development for studying human rna polymerase ii promoter proximal pausing
    Biophysical Journal, 2016
    Co-Authors: Yazan Alhadid, Dylan J Taatjes, Benjamin L Allen, Sangyoon Chung, Shimon Weiss
    Abstract:

    Promoter-proximal RNA Polymerase II (Pol-II) pausing has been shown to play a significant role in Transcription Regulation of elongating Pol-II complexes in a large number of metazoan and mammalian genes (1). The traditional understanding of Transcription Regulation in mammals involved controlling Pol-II recruitment to promoters and controlling initial steps at the promoter, including pre-initiation complex formation and promoter escape. Most works investigating promoter-proximal PolII pausing have employed chromatin immunoprecipitation followed by sequencing to determine Pol-II localization or in vitro Transcriptional assays using nuclear extracts analyzed with radioactive gel electrophoresis. In order to gain greater mechanistic insight into the Regulation of promoter-proximal Pol-II pausing, we use single molecule ALEX spectroscopy to monitor RNA transcripts production as function of composition and order of addition of Transcription factors to an in vitro reconstituted human Pol-II system. The RNA transcripts are detected by complementary doubly dye-labeled single-stranded DNA (ssDNA) probes. The human gene HSPA1B for heat shock protein 70 (Hsp70) is used as a model system due to its extensive characterization in drosophila. Our approach provides a rapid, sensitive and robust avenue for screening protein factors regulating promoter-proximal Pol-II pausing.1. H. Kwak, J. T. Lis, Control of Transcriptional elongation. Annu. Rev. Genet. 47, 483-508 (2013).

  • the mediator complex and Transcription Regulation
    Critical Reviews in Biochemistry and Molecular Biology, 2013
    Co-Authors: Zachary C Poss, Christopher C Ebmeier, Dylan J Taatjes
    Abstract:

    The Mediator complex is a multi-subunit assembly that appears to be required for regulating expression of most RNA polymerase II (pol II) transcripts, which include protein-coding and most non-coding RNA genes. Mediator and pol II function within the pre-initiation complex (PIC), which consists of Mediator, pol II, TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH and is approximately 4.0 MDa in size. Mediator serves as a central scaffold within the PIC and helps regulate pol II activity in ways that remain poorly understood. Mediator is also generally targeted by sequence-specific, DNA-binding Transcription factors (TFs) that work to control gene expression programs in response to developmental or environmental cues. At a basic level, Mediator functions by relaying signals from TFs directly to the pol II enzyme, thereby facilitating TF-dependent Regulation of gene expression. Thus, Mediator is essential for converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression). In this review, we summarize an expansive body of research on the Mediator complex, with an emphasis on yeast and mammalian complexes. We focus on the basics that underlie Mediator function, such as its structure and subunit composition, and describe its broad regulatory influence on gene expression, ranging from chromatin architecture to Transcription initiation and elongation, to mRNA processing. We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module.