Hot1 factor recruits co-activator Sub1 and elongation complex Spt4/5 to osmostress genes

2016 ◽  
Vol 473 (19) ◽  
pp. 3065-3079 ◽  
Author(s):  
M. Gomar-Alba ◽  
M. del Olmo
Keyword(s):  
Transcription Factor ◽  
Stress Response ◽  
Rna Polymerase Ii ◽  
Target Genes ◽  
Coding Region ◽  
Elongation Complex ◽  
Direct Role ◽  
Coding Regions ◽  
Stress Response Genes ◽  
Rule Out

Hyperosmotic stress response involves the adaptative mechanisms needed for cell survival. Under high osmolarity conditions, many stress response genes are activated by several unrelated transcription factors that are controlled by the Hog1 kinase. Osmostress transcription factor Hot1 regulates the expression of several genes involved in glycerol biosynthesis, and the presence of this transcription factor in their promoters is essential for RNApol II recruitment. The physical association between Hog1 and Hot1 activates this transcription factor and directs the RNA polymerase II localization at these promoters. We, herein, demonstrate that physical and genetic interactions exist between Hot1 and several proteins involved in transcriptional and posttranscriptional processes: for example, transcription co-activator Sub1 and elongation complex Spt4/5. The results presented in this work demonstrate that Hot1 enrichment is not detected through the coding regions of its target genes and rule out a direct role in transcription elongation. Instead, other data presented herein indicate a key function of the Hot1 transcription factor in the recruitment of these proteins to the promoter or the 5′-coding region of the genes under its control.

Elongin functions as a loading factor for Mediator at ATF6α-regulated ER stress response genes

2021 ◽  
Vol 118 (39) ◽  
pp. e2108751118
Author(s):  
Yanfeng He ◽  
Shigeo Sato ◽  
Chieri Tomomori-Sato ◽  
Shiyuan Chen ◽  
Zach H. Goode ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Stress Response ◽  
Er Stress ◽  
Rna Polymerase Ii ◽  
Transcription Activation ◽  
Bzip Transcription Factor ◽  
Er Stress Response ◽  
Stress Response Genes ◽  
Biochemical Studies ◽  
Rna Polymerase Ii Transcription

The bZIP transcription factor ATF6α is a master regulator of endoplasmic reticulum (ER) stress response genes. In this report, we identify the multifunctional RNA polymerase II transcription factor Elongin as a cofactor for ATF6α-dependent transcription activation. Biochemical studies reveal that Elongin functions at least in part by facilitating ATF6α-dependent loading of Mediator at the promoters and enhancers of ER stress response genes. Depletion of Elongin from cells leads to impaired transcription of ER stress response genes and to defects in the recruitment of Mediator and its CDK8 kinase subunit. Taken together, these findings bring to light a role for Elongin as a loading factor for Mediator during the ER stress response.

scholarly journals PICH, an ATP-dependent chromatin remodeling protein, transcriptionally co-regulates oxidative stress response.

2021 ◽  
Author(s):  
Anindita Dutta ◽  
Apurba Das ◽  
Deep Bisht ◽  
Vijendra Arya ◽  
Rohini Muthuswami
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Stress Response ◽  
Chromatin Remodeling ◽  
Dna Sequences ◽  
Target Genes ◽  
Antioxidant Response ◽  
Oxidative Stress Response ◽  
Antioxidant Genes

Cells respond to oxidative stress by elevating the levels of antioxidants, signaling, and transcriptional regulation often implemented by chromatin remodeling proteins.  The study presented in this paper shows that the expression of PICH, an ATP-dependent chromatin remodeler, is upregulated during oxidative stress in HeLa cells. We also show that PICH regulates the expression of Nrf2, a transcription factor regulating antioxidant response, both in the absence and presence of oxidative stress. In turn, Nrf2 regulates the expression of PICH in the presence of oxidative stress. Both PICH and Nrf2 together regulate the expression of antioxidant genes and this transcriptional regulation is dependent on the ATPase activity of PICH. In addition, H3K27ac modification also plays a role in activating transcription in the presence of oxidative stress. Co-immunoprecipitation experiments show that PICH and Nrf2 interact with H3K27ac in the presence of oxidative stress. Mechanistically, PICH recognizes ARE sequences present on its target genes and introduces a conformational change to the DNA sequences leading us to hypothesize that PICH regulates transcription by remodeling DNA. PICH ablation leads to reduced expression of Nrf2 and impaired antioxidant response leading to increased ROS content, thus, showing PICH is essential for the cell to respond to oxidative stress.

scholarly journals A Transcription Factor Pulse Can Prime Chromatin for Heritable Transcriptional Memory

2016 ◽  
Vol 37 (4) ◽  
Author(s):  
Aimee Iberg-Badeaux ◽  
Samuel Collombet ◽  
Benoit Laurent ◽  
Chris van Oevelen ◽  
Kuo-Kai Chin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Rna Polymerase Ii ◽  
Target Genes ◽  
Short Term Memory ◽  
Epigenetic Mechanism ◽  
Short Term ◽  
Term Memory ◽  
Pol Ii ◽  
Transcriptional Memory

ABSTRACT Short-term and long-term transcriptional memory is the phenomenon whereby the kinetics or magnitude of gene induction is enhanced following a prior induction period. Short-term memory persists within one cell generation or in postmitotic cells, while long-term memory can survive multiple rounds of cell division. We have developed a tissue culture model to study the epigenetic basis for long-term transcriptional memory (LTTM) and subsequently used this model to better understand the epigenetic mechanisms that enable heritable memory of temporary stimuli. We find that a pulse of transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) induces LTTM on a subset of target genes that survives nine cell divisions. The chromatin landscape at genes that acquire LTTM is more repressed than at those genes that do not exhibit memory, akin to a latent state. We show through chromatin immunoprecipitation (ChIP) and chemical inhibitor studies that RNA polymerase II (Pol II) elongation is important for establishing memory in this model but that Pol II itself is not retained as part of the memory mechanism. More generally, our work reveals that a transcription factor involved in lineage specification can induce LTTM and that failure to rerepress chromatin is one epigenetic mechanism underlying transcriptional memory.

scholarly journals DBC1, p300, HDAC3, and Siah1 coordinately regulate ELL stability and function for expression of its target genes

2020 ◽  
Vol 117 (12) ◽  
pp. 6509-6520 ◽  
Author(s):  
Subham Basu ◽  
Mahesh Barad ◽  
Dipika Yadav ◽  
Arijit Nandy ◽  
Bidisha Mukherjee ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Rna Polymerase Ii ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Elongation Factor ◽  
Diabetes Patient ◽  
Elongation Complex ◽  
Peripheral Blood Mononuclear ◽  
And Function

Among all of the Super Elongation Complex (SEC) components, ELL1 (also known as ELL) is the only bona fide elongation factor that directly stimulates transcription elongation by RNA polymerase II. However, the mechanism(s) of functional regulation of ELL1 (referred to as ELL hereafter), through its stabilization, is completely unknown. Here, we report a function of human DBC1 in regulating ELL stability involving HDAC3, p300, and Siah1. Mechanistically, we show that p300-mediated site-specific acetylation increases, whereas HDAC3-mediated deacetylation decreases, ELL stability through polyubiquitylation by the E3 ubiquitin ligase Siah1. DBC1 competes with HDAC3 for the same binding sites on ELL and thus increases its acetylation and stability. Knockdown of DBC1 reduces ELL levels and expression of a significant number of genes, including those involved in glucose metabolism. Consistently, Type 2 diabetes patient-derived peripheral blood mononuclear cells show reduced expression of DBC1 and ELL and associated key target genes required for glucose homeostasis. Thus, we describe a pathway of regulating stability and functions of key elongation factor ELL for expression of diverse sets of genes, including ones that are linked to Type 2 diabetes pathogenesis.

scholarly journals Histone Monoubiquitination in Chromatin Remodelling: Focus on the Histone H2B Interactome and Cancer

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3462
Author(s):  
Deborah J. Marsh ◽  
Yue Ma ◽  
Kristie-Ann Dickson
Keyword(s):  
Dna Damage ◽  
Rna Polymerase Ii ◽  
Target Genes ◽  
Chromatin Remodelling ◽  
Extensive Literature ◽  
Transcriptional Elongation ◽  
Post Translational Modification ◽  
Coding Region ◽  
Histone H2b ◽  
Related Proteins

Chromatin remodelling is a major mechanism by which cells control fundamental processes including gene expression, the DNA damage response (DDR) and ensuring the genomic plasticity required by stem cells to enable differentiation. The post-translational modification of histone H2B resulting in addition of a single ubiquitin, in humans at lysine 120 (K120; H2Bub1) and in yeast at K123, has key roles in transcriptional elongation associated with the RNA polymerase II-associated factor 1 complex (PAF1C) and in the DDR. H2Bub1 itself has been described as having tumour suppressive roles and a number of cancer-related proteins and/or complexes are recognised as part of the H2Bub1 interactome. These include the RING finger E3 ubiquitin ligases RNF20, RNF40 and BRCA1, the guardian of the genome p53, the PAF1C member CDC73, subunits of the switch/sucrose non-fermenting (SWI/SNF) chromatin remodelling complex and histone methyltransferase complexes DOT1L and COMPASS, as well as multiple deubiquitinases including USP22 and USP44. While globally depleted in many primary human malignancies, including breast, lung and colorectal cancer, H2Bub1 is selectively enriched at the coding region of certain highly expressed genes, including at p53 target genes in response to DNA damage, functioning to exercise transcriptional control of these loci. This review draws together extensive literature to cement a significant role for H2Bub1 in a range of human malignancies and discusses the interplay between key cancer-related proteins and H2Bub1-associated chromatin remodelling.

scholarly journals Phosphorylation and Maximal Activity of Saccharomyces cerevisiae Meiosis-Specific Transcription Factor Ndt80 Is Dependent on Ime2

2002 ◽  
Vol 22 (20) ◽  
pp. 7024-7040 ◽  
Author(s):  
Richelle Sopko ◽  
Sheetal Raithatha ◽  
David Stuart
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcription Factor ◽  
Target Genes ◽  
Meiotic Chromosome ◽  
Maximal Activity ◽  
Direct Role ◽  
Specific Transcription Factor ◽  
Mutant Strains ◽  
Sporulation Genes

ABSTRACT The Saccharomyces cerevisiae meiosis-specific transcription factor Ndt80 is responsible for the induction of a class of genes referred to as middle sporulation genes. Among the members of this family are the B-type cyclins and other genes whose products are required for meiotic chromosome division and spore morphogenesis. Inactivation of NDT80 leads to a failure to induce the middle sporulation genes and a subsequent arrest in pachytene. The expression of NDT80 is itself highly regulated. The initial transcription of NDT80 is dependent upon the protein kinase Ime2; once Ndt80 protein accumulates, it activates its own promoter, thus generating an autoactivation loop. In addition to being transcriptionally regulated, Ndt80 protein is posttranslationally regulated. Phosphorylation of Ndt80 occurs coincident with its activation as a transcription factor. If expressed prematurely in meiosis, Ndt80 accumulates initially in an unmodified form that is subsequently modified by phosphorylation. In contrast, Ndt80 expressed in ime2 mutant strains does not become modified and has a reduced ability to activate transcription of its target genes. Ime2 can also phosphorylate Ndt80 in vitro, further supporting a direct role for Ime2 in the phosphorylation of Ndt80. These data indicate that Ime2 plays a novel and previously unexpected role in promoting chromosome dissemination and progress through meiotic development by activating Ndt80.

scholarly journals The RAP74 Subunit of Human Transcription Factor IIF Has Similar Roles in Initiation and Elongation

1999 ◽  
Vol 19 (12) ◽  
pp. 8372-8382 ◽  
Author(s):  
Lei Lei ◽  
Delin Ren ◽  
Zachary F. Burton
Keyword(s):  
Transcription Factor ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Active Form ◽  
Elongation Complex ◽  
Allosteric Effector ◽  
Full Turn ◽  
Activated State ◽  
Transcription Factor Iif ◽  
Promoter Dna

ABSTRACT Transcription factor IIF (TFIIF) is a protein allosteric effector for RNA polymerase II during the initiation and elongation phases of the transcription cycle. In initiation, TFIIF induces promoter DNA to wrap almost a full turn around RNA polymerase II in a complex that includes the general transcription factors TATA-binding protein, TFIIB, and TFIIE. During elongation, TFIIF also supports a more active conformation of RNA polymerase II. This conformational model for elongation is supported by three lines of experimental evidence. First, a region within the RNA polymerase II-associating protein 74 (RAP74) subunit of TFIIF (amino acids T154 to M177), a region that is critical for isomerization of the preinitiation complex, is also critical for elongation stimulation. Amino acid substitutions within this region are shown to have very similar effects on initiation and elongation, and mutagenic analysis indicates that L155, W164, N172, I176, and M177 are the most important residues in this region for transcription. Second, TFIIF is shown to have a higher affinity for rapidly elongating RNA polymerase II than for the stalled elongation complex, indicating that RNA polymerase II alternates between active and inactive states during elongation and that TFIIF stimulates elongation by supporting the active conformational state of RNA polymerase II. The deleterious I176A substitution in the critical region of RAP74 decreases the affinity of TFIIF for the active form of the elongation complex. Third, TFIIF is shown by Arrhenius analysis to stimulate elongation by populating an activated state of RNA polymerase II.

Interaction of MLL Amino Terminal Sequences with Menin Is Required for Transformation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 664-664
Author(s):  
Jay L. Hess ◽  
Zhaohai Yang ◽  
Haoren Wang ◽  
Ya-Xiong Chen ◽  
Thomas A. Milne ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Rna Polymerase Ii ◽  
Fusion Proteins ◽  
Target Genes ◽  
Hox Genes ◽  
Dominant Negative ◽  
Similar Distribution ◽  
Genetic Ablation ◽  
Amino Terminal ◽  
Coding Regions

Abstract Rearrangements of the mixed lineage leukemia gene MLL are associated with aggressive lymphoid and myeloid leukemias. The resulting MLL fusion proteins enforce high-level expression of HOX genes including HOX A7 and HOX A9 and the HOX cofactor MEIS1, which is pivotal for leukemogenesis. The mechanism by which this occurs and the relationship to normal MLL function is unknown. MLL and MLL fusion proteins bind with a similar distribution in hematopoietic cells at both promoters and coding sequences of target genes. Our studies suggest that a major mechanism of regulating MLL, which is expressed throughout hematopoiesis, is through modulating it’s binding to target promoters. MLL binds directly to the promoters and coding regions of HOX A7, HOX A9, and MEIS1 only in myeloblasts and not in neutrophils, indicating MLL is physically associated with genes only when they are actively transcribed. Expression of A cluster HOX loci and MEIS1 remains persistently elevated when MLL-ENL or dimerized MLL fusion proteins are expressed. Expression of either fusion protein is associated with increased binding of wild type MLL accompanied by increases in histone acetylation and histone H3 lysine 4, marks that are normally almost completely erased during myeloid differentiation. In addition MLL-ENL induces increased lysine 79 methylation. Both MLL and MLL fusion proteins interact with the tumor suppressor menin via sequences in the extreme amino terminus of MLL. In addition both proteins physically interact with RNA polymerase II, which shows abnormal pausing in the coding regions of HOX genes in Mll null cells. Genetic ablation of menin or expression of a dominant negative inhibitor of the MLL-menin interaction inhibits the growth of MLL fusion protein transformed cells. These findings suggest MLL fusion proteins act in concert with menin, MLL and other coactivators to deregulate HOX gene expression pivotal for transformation.

scholarly journals Network Analysis of Local Gene Regulators in Arabidopsis thaliana under Spaceflight Stress

Computers ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 18
Author(s):  
Vidya Manian ◽  
Harshini Gangapuram ◽  
Jairo Orozco ◽  
Heeralal Janwa ◽  
Carlos Agrinsoni
Keyword(s):  
Arabidopsis Thaliana ◽  
Stress Response ◽  
Network Analysis ◽  
Target Genes ◽  
Carbon Fixation ◽  
Reduction Process ◽  
Centrality Measures ◽  
Lasso Regression ◽  
Gene Expressions ◽  
Stress Response Genes

Spaceflight microgravity affects normal plant growth in several ways. The transcriptional dataset of the plant model organism Arabidopsis thaliana grown in the international space station is mined using graph-theoretic network analysis approaches to identify significant gene transcriptions in microgravity essential for the plant’s survival and growth in altered environments. The photosynthesis process is critical for the survival of the plants in spaceflight under different environmentally stressful conditions such as lower levels of gravity, lesser oxygen availability, low atmospheric pressure, and the presence of cosmic radiation. Lasso regression method is used for gene regulatory network inferencing from gene expressions of four different ecotypes of Arabidopsis in spaceflight microgravity related to the photosynthetic process. The individual behavior of hub-genes and stress response genes in the photosynthetic process and their impact on the whole network is analyzed. Logistic regression on centrality measures computed from the networks, including average shortest path, betweenness centrality, closeness centrality, and eccentricity, and the HITS algorithm is used to rank genes and identify interactor or target genes from the networks. Through the hub and authority gene interactions, several biological processes associated with photosynthesis and carbon fixation genes are identified. The altered conditions in spaceflight have made all the ecotypes of Arabidopsis sensitive to dehydration-and-salt stress. The oxidative and heat-shock stress-response genes regulate the photosynthesis genes that are involved in the oxidation-reduction process in spaceflight microgravity, enabling the plant to adapt successfully to the spaceflight environment.

scholarly journals DAF-16/FOXO requires Protein Phosphatase 4 to initiate transcription of stress resistance and longevity promoting genes

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ilke Sen ◽  
Xin Zhou ◽  
Alexey Chernobrovkin ◽  
Nataly Puerta-Cavanzo ◽  
Takaharu Kanno ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Rna Polymerase Ii ◽  
Stress Resistance ◽  
Protein Phosphatase ◽  
Target Genes ◽  
Transcriptional Regulator ◽  
Specific Protein ◽  
Transcriptional Initiation ◽  
C Elegans ◽  
Rate Limiting

AbstractIn C. elegans, the conserved transcription factor DAF-16/FOXO is a powerful aging regulator, relaying dire conditions into expression of stress resistance and longevity promoting genes. For some of these functions, including low insulin/IGF signaling (IIS), DAF-16 depends on the protein SMK-1/SMEK, but how SMK-1 exerts this role has remained unknown. We show that SMK-1 functions as part of a specific Protein Phosphatase 4 complex (PP4SMK-1). Loss of PP4SMK-1 hinders transcriptional initiation at several DAF-16-activated genes, predominantly by impairing RNA polymerase II recruitment to their promoters. Search for the relevant substrate of PP4SMK-1 by phosphoproteomics identified the conserved transcriptional regulator SPT-5/SUPT5H, whose knockdown phenocopies the loss of PP4SMK-1. Phosphoregulation of SPT-5 is known to control transcriptional events such as elongation and termination. Here we also show that transcription initiating events are influenced by the phosphorylation status of SPT-5, particularly at DAF-16 target genes where transcriptional initiation appears rate limiting, rendering PP4SMK-1 crucial for many of DAF-16’s physiological roles.

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