scholarly journals SUMO and Transcriptional Regulation: The Lessons of Large-Scale Proteomic, Modifomic and Genomic Studies

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 828
Author(s):  
Mathias Boulanger ◽  
Mehuli Chakraborty ◽  
Denis Tempé ◽  
Marc Piechaczyk ◽  
Guillaume Bossis
Keyword(s):  
Large Scale ◽  
Transcriptional Control ◽  
Pol Ii ◽  
Pol I ◽  
New Concepts ◽  
Gene Expression Control ◽  
Genomic Studies ◽  
Transcriptional Coregulators ◽  
Pol Iii

One major role of the eukaryotic peptidic post-translational modifier SUMO in the cell is transcriptional control. This occurs via modification of virtually all classes of transcriptional actors, which include transcription factors, transcriptional coregulators, diverse chromatin components, as well as Pol I-, Pol II- and Pol III transcriptional machineries and their regulators. For many years, the role of SUMOylation has essentially been studied on individual proteins, or small groups of proteins, principally dealing with Pol II-mediated transcription. This provided only a fragmentary view of how SUMOylation controls transcription. The recent advent of large-scale proteomic, modifomic and genomic studies has however considerably refined our perception of the part played by SUMO in gene expression control. We review here these developments and the new concepts they are at the origin of, together with the limitations of our knowledge. How they illuminate the SUMO-dependent transcriptional mechanisms that have been characterized thus far and how they impact our view of SUMO-dependent chromatin organization are also considered.

scholarly journals RNA polymerase I (Pol I) passage through nucleosomes depends on Pol I subunits binding its lobe structure

2020 ◽  
Vol 295 (15) ◽  
pp. 4782-4795 ◽  
Author(s):  
Philipp E. Merkl ◽  
Michael Pilsl ◽  
Tobias Fremter ◽  
Katrin Schwank ◽  
Christoph Engel ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase I ◽  
Dna Templates ◽  
Pol Ii ◽  
Naked Dna ◽  
Pol I ◽  
Intrinsic Capacity ◽  
Pol Iii ◽  
Polymerase I

RNA polymerase I (Pol I) is a highly efficient enzyme specialized in synthesizing most ribosomal RNAs. After nucleosome deposition at each round of rDNA replication, the Pol I transcription machinery has to deal with nucleosomal barriers. It has been suggested that Pol I–associated factors facilitate chromatin transcription, but it is unknown whether Pol I has an intrinsic capacity to transcribe through nucleosomes. Here, we used in vitro transcription assays to study purified WT and mutant Pol I variants from the yeast Saccharomyces cerevisiae and compare their abilities to pass a nucleosomal barrier with those of yeast Pol II and Pol III. Under identical conditions, purified Pol I and Pol III, but not Pol II, could transcribe nucleosomal templates. Pol I mutants lacking either the heterodimeric subunit Rpa34.5/Rpa49 or the C-terminal part of the specific subunit Rpa12.2 showed a lower processivity on naked DNA templates, which was even more reduced in the presence of a nucleosome. Our findings suggest that the lobe-binding subunits Rpa34.5/Rpa49 and Rpa12.2 facilitate passage through nucleosomes, suggesting possible cooperation among these subunits. We discuss the contribution of Pol I–specific subunit domains to efficient Pol I passage through nucleosomes in the context of transcription rate and processivity.

scholarly journals Critical role of deadenylation in regulating poly(A) rhythms and circadian gene expression

2019 ◽  
Author(s):  
Xiangyu Yao ◽  
Shihoko Kojima ◽  
Jing Chen
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Transcriptional Control ◽  
Critical Role ◽  
Tail Length ◽  
Circadian Gene ◽  
Gene Expression Control ◽  
Rhythmic Gene ◽  
Transcriptional Controls

AbstractThe mammalian circadian clock is deeply rooted in rhythmic regulation of gene expression. Rhythmic transcriptional control mediated by the circadian transcription factors is thought to be the main driver of mammalian circadian gene expression. However, mounting evidence has demonstrated the importance of rhythmic post-transcriptional controls, and it remains unclear how the transcriptional and post-transcriptional mechanisms collectively control rhythmic gene expression. A recent study discovered rhythmicity in poly(A) tail length in mouse liver and its strong correlation with protein expression rhythms. To understand the role of rhythmic poly(A) regulation in circadian gene expression, we constructed a parsimonious model that depicts rhythmic control imposed upon basic mRNA expression and poly(A) regulation processes, including transcription, deadenylation, polyadenylation, and degradation. The model results reveal the rhythmicity in deadenylation as the strongest contributor to the rhythmicity in poly(A) tail length and the rhythmicity in the abundance of the mRNA subpopulation with long poly(A) tails (a rough proxy for mRNA translatability). In line with this finding, the model further shows that the experimentally observed distinct peak phases in the expression of deadenylases, regardless of other rhythmic controls, can robustly group the rhythmic mRNAs by their peak phases in poly(A) tail length and in abundance of the subpopulation with long poly(A) tails. This provides a potential mechanism to synchronize the phases of target gene expression regulated by the same deadenylases. Our findings highlight the critical role of rhythmic deadenylation in regulating poly(A) rhythms and circadian gene expression.Author SummaryThe biological circadian clock regulates various bodily functions such that they anticipate and respond to the day-and-night cycle. To achieve this, the circadian clock controls rhythmic gene expression, and these genes ultimately drive the rhythmicity of downstream biological processes. As a mechanism of driving circadian gene expression, rhythmic transcriptional control has attracted the central focus. However, mounting evidence has also demonstrated the importance of rhythmic post-transcriptional controls. Here we use mathematical modeling to investigate how transcriptional and post-transcriptional rhythms coordinately control rhythmic gene expression. We have particularly focused on rhythmic regulation of the length of poly(A) tail, a nearly universal feature of mRNAs that controls mRNA stability and translation. Our model reveals that the rhythmicity of deadenylation, the process that shortens the poly(A) tail, is the dominant contributor to the rhythmicity in poly(A) tail length and mRNA translatability. Particularly, the phase of deadenylation nearly overrides the other rhythmic processes in controlling the phases of poly(A) tail length and mRNA translatability. Our finding highlights the critical role of rhythmic deadenylation in circadian gene expression control.

scholarly journals Large-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels

2010 ◽  
Vol 19 (9) ◽  
pp. 1863-1872 ◽  
Author(s):  
M. Barbalic ◽  
J. Dupuis ◽  
A. Dehghan ◽  
J. C. Bis ◽  
R. C. Hoogeveen ◽  
...  
Keyword(s):  
Large Scale ◽  
Genomic Studies

scholarly journals A TATA-Binding Protein Mutant Defective for TFIID Complex Formation In Vivo

1999 ◽  
Vol 19 (6) ◽  
pp. 3951-3957 ◽  
Author(s):  
Ryan T. Ranallo ◽  
Kevin Struhl ◽  
Laurie A. Stargell
Keyword(s):  
Binding Protein ◽  
Tata Binding Protein ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Pol Ii ◽  
Pol I ◽  
Pol Iii ◽  
Polymerase I ◽  
Tfiid Complex

ABSTRACT Using an intragenic complementation screen, we have identified a temperature-sensitive TATA-binding protein (TBP) mutant (K151L,K156Y) that is defective for interaction with certain yeast TBP-associated factors (TAFs) at the restrictive temperature. The K151L,K156Y mutant appears to be functional for RNA polymerase I (Pol I) and Pol III transcription, and it is capable of supporting Gal4-activated and Gcn4-activated transcription by Pol II. However, transcription from certain TATA-containing and TATA-less Pol II promoters is reduced at the restrictive temperature. Immunoprecipitation analysis of extracts prepared after culturing cells at the restrictive temperature for 1 h indicates that the K151L,K156Y derivative is severely compromised in its ability to interact with TAF130, TAF90, TAF68/61, and TAF25 while remaining functional for interaction with TAF60 and TAF30. Thus, a TBP mutant that is compromised in its ability to form TFIID can support the response to Gcn4 but is defective for transcription from specific promoters in vivo.

scholarly journals Myanmar Burkholderia pseudomallei strains are genetically diverse and originate from Asia with phylogenetic evidence of reintroductions from neighbouring countries

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jessica R. Webb ◽  
Mo Mo Win ◽  
Khwar Nyo Zin ◽  
Kyi Kyi Nyein Win ◽  
Thin Thin Wah ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Southeast Asia ◽  
Burkholderia Pseudomallei ◽  
Large Scale ◽  
Environmental Isolates ◽  
Dynamic Nature ◽  
Recent Event ◽  
Asian Clade ◽  
Genomic Studies

Abstract Melioidosis was first identified in Myanmar in 1911 but for the last century it has remained largely unreported there. Burkholderia pseudomallei was first isolated from the environment of Myanmar in 2016, confirming continuing endemicity. Recent genomic studies showed that B. pseudomallei originated in Australia and spread to Asia, with phylogenetic evidence of repeated reintroduction of B. pseudomallei across countries bordered by the Mekong River and the Malay Peninsula. We present the first whole-genome sequences of B. pseudomallei isolates from Myanmar: nine clinical and seven environmental isolates. We used large-scale comparative genomics to assess the genetic diversity, phylogeography and potential origins of B. pseudomallei in Myanmar. Global phylogenetics demonstrated that Myanmar isolates group in two distantly related clades that reside in a more ancestral Asian clade with high amounts of genetic diversity. The diversity of B. pseudomallei from Myanmar and divergence within our global phylogeny suggest that the original introduction of B. pseudomallei to Myanmar was not a recent event. Our study provides new insights into global patterns of B. pseudomallei dissemination, most notably the dynamic nature of movement of B. pseudomallei within densely populated Southeast Asia. The role of anthropogenic influences in both ancient and more recent dissemination of B. pseudomallei to Myanmar and elsewhere in Southeast Asia and globally requires further study.

scholarly journals The Potential Role of Genomic Medicine in the Therapeutic Management of Rheumatoid Arthritis

2019 ◽  
Vol 8 (6) ◽  
pp. 826 ◽  
Author(s):  
Marialbert Acosta-Herrera ◽  
David González-Serna ◽  
Javier Martín
Keyword(s):  
Rheumatoid Arthritis ◽  
Large Scale ◽  
Rare Variants ◽  
Drug Repositioning ◽  
Genomic Medicine ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Genomic Studies ◽  
The Right

During the last decade, important advances have occurred regarding understanding of the pathogenesis and treatment of rheumatoid arthritis (RA). Nevertheless, response to treatment is not universal, and choosing among different therapies is currently based on a trial and error approach. The specific patient’s genetic background influences the response to therapy for many drugs: In this sense, genomic studies on RA have produced promising insights that could help us find an effective therapy for each patient. On the other hand, despite the great knowledge generated regarding the genetics of RA, most of the investigations performed to date have focused on identifying common variants associated with RA, which cannot explain the complete heritability of the disease. In this regard, rare variants could also contribute to this missing heritability as well as act as biomarkers that help in choosing the right therapy. In the present article, different aspects of genetics in the pathogenesis and treatment of RA are reviewed, from large-scale genomic studies to specific rare variant analyses. We also discuss the shared genetic architecture existing among autoimmune diseases and its implications for RA therapy, such as drug repositioning.

The phylogenetic relations of DNA-dependent RNA polymerases of archaebacteria, eukaryotes, and eubacteria

1989 ◽  
Vol 35 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Wolfram Zillig ◽  
Hans-Peter Klenk ◽  
Peter Palm ◽  
Gabriela Pühler ◽  
Felix Gropp ◽  
...  
Keyword(s):  
Nuclear Genome ◽  
Distance Matrix ◽  
Gene Organization ◽  
Amino Acid Sequences ◽  
Rna Polymerases ◽  
Matrix Analysis ◽  
Pol Ii ◽  
Phylogenetic Relations ◽  
Pol I ◽  
Pol Iii

Unrooted phylogenetic dendrograms were calculated by two independent methods, parsimony and distance matrix analysis, from an alignment of the derived amino acid sequences of the A and C subunits of the DNA-dependent RNA polymerases of the archaebacteria Sulfolobus acidocaldarius and Halobacterium halobium with 12 corresponding sequences including a further set of archaebacterial A + C subunits, eukaryotic nuclear RNA polymerases, pol I, pol II, and pol III, eubacterial β′ and chloroplast β′ and β″ subunits. They show the archaebacteria as a coherent group in close neighborhood of and sharing a bifurcation with eukaryotic pol II and (or) pol IIIA components. The most probable trees show pol IA branching off from the tree separately at a bifurcation with the eubacterial β′ lineage. The implications of these results, especially for understanding the possibly chimeric origin of the eukaryotic nuclear genome, are discussed.Key words: transcription, evolution, taxonomy, subunits, gene organization.

scholarly journals The promoter for the procyclic acidic repetitive protein (PARP) genes of Trypanosoma brucei shares features with RNA polymerase I promoters.

1992 ◽  
Vol 12 (6) ◽  
pp. 2644-2652 ◽  
Author(s):  
S D Brown ◽  
J Huang ◽  
L H Van der Ploeg
Keyword(s):  
Rna Polymerase ◽  
Transcription Initiation ◽  
Initiation Site ◽  
Transcription Initiation Site ◽  
Protein Coding ◽  
Pol Ii ◽  
Protein Coding Genes ◽  
Pol I ◽  
Pol Iii ◽  
Repetitive Protein

All eukaryotic protein-coding genes are believed to be transcribed by RNA polymerase (Pol) II. An exception may exist in the protozoan parasite Trypanosoma brucei, in which the genes encoding the variant surface glycoprotein (VSG) and procyclic acidic repetitive protein (PARP) are transcribed by an RNA polymerase that is resistant to the Pol II inhibitor alpha-amanitin. The PARP and VSG genes were proposed to be transcribed by Pol I (C. Shea, M. G.-S. Lee, and L. H. T. Van der Ploeg, Cell 50:603-612, 1987; G. Rudenko, M. G.-S. Lee, and L. H. T. Van der Ploeg, Nucleic Acids Res. 20:303-306, 1992), a suggestion that has been substantiated by the finding that trypanosomes can transcribe protein-coding genes by Pol I (G. Rudenko, H.-M. Chung, V. P. Pham, and L. H. T. Van der Ploeg, EMBO J. 10:3387-3397, 1991). We analyzed the sequence elements of the PARP promoter by linker scanning mutagenesis and compared the PARP promoter with Pol I, Pol II, and Pol III promoters. The PARP promoter appeared to be of limited complexity and contained at least two critical regions. The first was located adjacent to the transcription initiation site (nucleotides [nt] -69 to +12) and contained three discrete domains in which linker scanning mutants affected the transcriptional efficiency: at nt -69 to -56, -37 to -11, and -11 to +12. The second region was located between nt -140 and -131, and a third region may be located between nt -228 and -205. The nucleotide sequences of these elements, and their relative positioning with respect to the transcription initiation site did not resemble those of either Pol II or Pol III promoter elements, but rather reflected the organization of Pol I promoters in (i) similarity in the positioning of essential domains in the PARP promoter and Pol I promoter, (ii) strong sequence homology between the PARP core promoter element (nt -37 to -11) and identically positioned nucleotide sequences in the trypanosome rRNA and VSG gene promoters, and (iii) moderate effects on promoter activity of mutations around the transcription initiation site.

scholarly journals Cyclin-Dependent Kinases and CTD Phosphatases in Cell Cycle Transcriptional Control: Conservation across Eukaryotic Kingdoms and Uniqueness to Plants

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 279
Author(s):  
Zhi-Liang Zheng
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase Ii ◽  
Large Scale ◽  
Transcriptional Control ◽  
Cell Cycle Control ◽  
Yeast Saccharomyces Cerevisiae ◽  
Pol Ii ◽  
Precise Control ◽  
Cyclin Dependent Kinases ◽  
Entire Cell

Cell cycle control is vital for cell proliferation in all eukaryotic organisms. The entire cell cycle can be conceptually separated into four distinct phases, Gap 1 (G1), DNA synthesis (S), G2, and mitosis (M), which progress sequentially. The precise control of transcription, in particular, at the G1 to S and G2 to M transitions, is crucial for the synthesis of many phase-specific proteins, to ensure orderly progression throughout the cell cycle. This mini-review highlights highly conserved transcriptional regulators that are shared in budding yeast (Saccharomyces cerevisiae), Arabidopsis thaliana model plant, and humans, which have been separated for more than a billion years of evolution. These include structurally and/or functionally conserved regulators cyclin-dependent kinases (CDKs), RNA polymerase II C-terminal domain (CTD) phosphatases, and the classical versus shortcut models of Pol II transcriptional control. A few of CDKs and CTD phosphatases counteract to control the Pol II CTD Ser phosphorylation codes and are considered critical regulators of Pol II transcriptional process from initiation to elongation and termination. The functions of plant-unique CDKs and CTD phosphatases in relation to cell division are also briefly summarized. Future studies towards testing a cooperative transcriptional mechanism, which is proposed here and involves sequence-specific transcription factors and the shortcut model of Pol II CTD code modulation, across the three eukaryotic kingdoms will reveal how individual organisms achieve the most productive, large-scale transcription of phase-specific genes required for orderly progression throughout the entire cell cycle.

scholarly journals Analysis of the Caenorhabditis elegans rpc-1 gene

2005 ◽  
Author(s):  
◽  
Qun Zheng
Keyword(s):  
Gene Expression ◽  
Promoter Activity ◽  
Rna Polymerase Iii ◽  
Transgenic Animals ◽  
Rna Polymerases ◽  
Pol Ii ◽  
C Elegans ◽  
Pol I ◽  
Genes Encoding ◽  
Pol Iii

In eukaryotes, two large subunits form the core catalytic structure of RNA polymerase III (Pol III), which is conserved in other RNA polymerases, Pol I and Pol II. It has been found that Pol III activity is tightly associated to cell growth. TFIII B has been shown to be one of main mediators in this process. No regulation of the Pol III largest subunit gene has been found. In C. elegans, the rpc-1 gene encodes the largest subunit of Pol III. Here, I identified two critical structural components of RPC-1, Gly644 and Gly1055, whose mutations result in larval lethal arrestment. These two amino acid residues are universally conserved in RNA polymerases, indicating their overall involvement in gene transcription mechanism. Also, I found that maternally inherited, not embryonically expressed, rpc-1 gene products survive early development. Starvation was found to suppress rpc-1 gene expression and re-feeding treatment enhances rpc-1 gene expression rapidly. No similar regulation was detected in genes encoding largest subunits of Pol I and Pol II. This is the first time that rpc-1 gene regulation has been reported. Insulin signaling may not be involved in this regulation. Also, I found that rpc-1 promoter is not ubiquitously active in C. elegans. Using the rpc-1p::gfp transgene, the rpc-1 promoter activity is only detected in a subset of neurons in the head and the tail and the intestine. While starvation silences the rpc-1 promoter activity in most tissues and cells, ASK neurons still show GFP staining in the rpc-1p::gfp transgenic animals, indicating that rpc-1 transcription in ASK neurons is continuously active under starvation conditions. Further studies suggest that TGF-[beta] signaling is involved in mediating the rpc-1 promoter activity in ASK neurons.

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