Plant adjustment to environmental changes involves complex crosstalk between extrinsic and intrinsic cues. In the past two decades, extensive research has elucidated the key roles of PHYTOCHROME-INTERACTING FACTOR4 (PIF4) and the phytohormone auxin in thermomorphogenesis. In this study, we identified a previously unexplored role of jasmonate (JA) signaling components, the Mediator complex, and their integration with auxin signaling during thermomorphogenesis in Arabidopsis (Arabidopsis thaliana). Warm temperature induces expression of JA signaling genes including MYC2, but, surprisingly, this transcriptional activation is not JA dependent. Warm temperature also promotes accumulation of the JA signaling receptor CORONATINE INSENSITIVE1 (COI1) and degradation of the JA signaling repressor JASMONATE-ZIM-DOMAIN PROTEIN9, which probably leads to de-repression of MYC2, enabling it to contribute to the expression of MEDIATOR SUBUNIT17 (MED17). In response to warm temperature, MED17 occupies the promoters of thermosensory genes including PIF4, YUCCA8 (YUC8), INDOLE-3-ACETIC ACID INDUCIBLE19 (IAA19), and IAA29. Moreover, MED17 facilitates enrichment of H3K4me3 on the promoters of PIF4, YUC8, IAA19, and IAA29 genes. Interestingly, both occupancy of MED17 and enrichment of H3K4me3 on these thermomorphogenesis-related promoters are dependent on PIF4 (or PIFs). Altered accumulation of COI1 under warm temperature in the med17 mutant suggests the possibility of a feedback mechanism. Overall, this study reveals the role of the Mediator complex as an integrator of JA and auxin signaling pathways during thermomorphogenesis.

• MeSH
• Arabidopsis * metabolismus   MeSH
• cyklopentany metabolismus   MeSH
• kyseliny indoloctové metabolismus   MeSH
• mediátorový komplex metabolismus   MeSH
• oxylipiny metabolismus   MeSH
• proteiny huseníčku * metabolismus   MeSH
• regulace genové exprese u rostlin MeSH
• signální transdukce MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyklopentany MeSH
• jasmonic acid MeSH Prohlížeč
• kyseliny indoloctové MeSH
• mediátorový komplex MeSH
• oxylipiny MeSH
• proteiny huseníčku * MeSH

Cellular leiomyoma (CL) represents an uncommon variant of uterine leiomyoma with limited data concerning its immunohistochemical and molecular profile. We performed a comprehensive analysis of 52 CL cases all of which were analyzed immunohistochemically. Molecular analysis was possible in 32 cases with sufficient DNA, and 38 cases with sufficient RNA. The immunohistochemical results showed a high expression of smooth muscle markers (calponin (100%), desmin (100%), smooth muscle actin (98.1%), caldesmon (96.1%), transgelin (96.1%), smooth muscle myosin heavy chain (86.5%), and smoothelin (61.5%)). Concerning markers of endometrial stromal differentiation, the expression of CD10 was observed in 65.4% cases (42.2% with H-score > 50), and IFITM1 in 36.5% cases (1.9% with H-score > 50). 36.5% showed HMGA2 overexpression at the IHC level, associated with increased mRNA expression in 14/14 cases. The rearrangement of the HMGA2 gene was detected in 13.2%. Chromosome 1p deletion was found in 19.3%, while 9.4% of tumors showed a pathogenic mutation in the MED12 gene. In conclusion, CL is immunohistochemically characterized by a high expression of "smooth muscle" markers commonly associated with a co-expression of "endometrial stromal" markers, where IFITM1 shows superior performance compared to CD10 regarding its specificity for differentiation from endometrial stromal tumors. The sensitivity of smoothelin in CL seems rather low, but no data is available to assess its specificity. On a molecular level, the most common mutually exclusive aberration in CL affects HMGA2, followed by chromosome 1p deletions and MED12 mutations.

• Klíčová slova
• Cellular leiomyoma, Chromosome 1p, HMGA2, MED12, NGS, ddPCR,
• MeSH
• chromozomy chemie   metabolismus   MeSH
• leiomyom * patologie   MeSH
• lidé MeSH
• mediátorový komplex genetika   metabolismus   MeSH
• mutace MeSH
• nádory dělohy * patologie   MeSH
• nádory endometria * genetika   MeSH
• neprilysin analýza   MeSH
• protein HMGA2 MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• HMGA2 protein, human MeSH Prohlížeč
• MED12 protein, human MeSH Prohlížeč
• mediátorový komplex MeSH
• neprilysin MeSH
• protein HMGA2 MeSH

Mediator, a multisubunit protein complex, is a signal processor that conveys regulatory information from transcription factors to RNA polymerase II and therefore plays an important role in the regulation of gene expression. This megadalton complex comprises four modules, namely, the head, middle, tail, and kinase modules. The first three modules form the core part of the complex, whereas association of the kinase module is facultative. The kinase module is able to alter the function of Mediator and has been established as a major transcriptional regulator of numerous developmental and biochemical processes. The kinase module consists of MED12, MED13, CycC, and kinase CDK8. Upon association with Mediator, the kinase module can alter its structure and function dramatically. In the past decade, research has established that the kinase module is very important for plant growth and development, and in the fight against biotic and abiotic challenges. However, there has been no comprehensive review discussing these findings in detail and depth. In this review, we survey the regulation of kinase module subunits and highlight their many functions in plants. Coordination between the subunits to process different signals for optimum plant growth and development is also discussed.

• Klíčová slova
• Arabidopsis, Mediator complex, RNA polymerase II, development, kinase module, transcription,
• MeSH
• cyklin-dependentní kinasa 8 * genetika   metabolismus   MeSH
• mediátorový komplex * genetika   metabolismus   MeSH
• rostliny metabolismus   MeSH
• transkripční faktory metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cyklin-dependentní kinasa 8 * MeSH
• mediátorový komplex * MeSH
• transkripční faktory MeSH

The mediator (MED) represents a large, conserved, multi-subunit protein complex that regulates gene expression through interactions with RNA polymerase II and enhancer-bound transcription factors. Expanding research accomplishments suggest the predominant role of plant MED subunits in the regulation of various physiological and developmental processes, including the biotic stress response against bacterial and fungal pathogens. However, the involvement of MED subunits in virus/viroid pathogenesis remains elusive. In this study, we investigated for the first time the gene expression modulation of selected MED subunits in response to five viroid species (Apple fruit crinkle viroid (AFCVd), Citrus bark cracking viroid (CBCVd), Hop latent viroid (HLVd), Hop stunt viroid (HSVd), and Potato spindle tuber viroid (PSTVd)) in two model plant species (Nicotiana tabacum and N. benthamiana) and a commercially important hop (Humulus lupulus) cultivar. Our results showed a differential expression pattern of MED subunits in response to a viroid infection. The individual plant MED subunits displayed a differential and tailored expression pattern in response to different viroid species, suggesting that the MED expression is viroid- and plant species-dependent. The explicit evidence obtained from our results warrants further investigation into the association of the MED subunit with symptom development. Together, we provide a comprehensive portrait of MED subunit expression in response to viroid infection and a plausible involvement of MED subunits in fine-tuning transcriptional reprogramming in response to viroid infection, suggesting them as a potential candidate for rewiring the defense response network in plants against pathogens.

• Klíčová slova
• Nicotiana benthamiana, Nicotiana tabacum, differential expression, hop, mediator complex, pathogen, quantitative reverse transcription PCR, viroid,
• MeSH
• druhová specificita MeSH
• Humulus genetika   virologie   MeSH
• listy rostlin genetika   mikrobiologie   MeSH
• mediátorový komplex genetika   MeSH
• regulace genové exprese u rostlin MeSH
• rostlinné proteiny genetika   MeSH
• rostlinné viry MeSH
• stanovení celkové genové exprese MeSH
• tabák genetika   virologie   MeSH
• viroidy genetika   patogenita   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mediátorový komplex MeSH
• rostlinné proteiny MeSH

Stem rust is an important disease of wheat that can be controlled using resistance genes. The gene SuSr-D1 identified in cultivar 'Canthatch' suppresses stem rust resistance. SuSr-D1 mutants are resistant to several races of stem rust that are virulent on wild-type plants. Here we identify SuSr-D1 by sequencing flow-sorted chromosomes, mutagenesis, and map-based cloning. The gene encodes Med15, a subunit of the Mediator Complex, a conserved protein complex in eukaryotes that regulates expression of protein-coding genes. Nonsense mutations in Med15b.D result in expression of stem rust resistance. Time-course RNAseq analysis show a significant reduction or complete loss of differential gene expression at 24 h post inoculation in med15b.D mutants, suggesting that transcriptional reprogramming at this time point is not required for immunity to stem rust. Suppression is a common phenomenon and this study provides novel insight into suppression of rust resistance in wheat.

• MeSH
• Basidiomycota patogenita   MeSH
• chromozomy rostlin genetika   MeSH
• duplikace genu MeSH
• exprese genu MeSH
• fenotyp MeSH
• imunita rostlin genetika   MeSH
• lipnicovité klasifikace   genetika   MeSH
• mapování chromozomů MeSH
• mediátorový komplex genetika   MeSH
• mutace MeSH
• nemoci rostlin genetika   imunologie   mikrobiologie   MeSH
• odolnost vůči nemocem genetika   MeSH
• pšenice genetika   imunologie   mikrobiologie   MeSH
• regulace genové exprese u rostlin MeSH
• rostlinné geny genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• mediátorový komplex MeSH

Transcription factors exert their regulatory potential on RNA polymerase II machinery through a multiprotein complex called Mediator complex or Mediator. The Mediator complex integrates regulatory signals from cell regulatory cascades with the regulation by transcription factors. The Mediator complex consists of 25 subunits in Saccharomyces cerevisiae and 30 or more subunits in multicellular eukaryotes. Mediator subunit 28 (MED28), along with MED30, MED23, MED25 and MED26, belong to presumably evolutionarily new subunits that seem to be absent in unicellular eukaryotes and are likely to have evolved together with multicellularity and cell differentiation. Previously, we have shown that an originally uncharacterized predicted gene, F28F8.5, is the true MED28 orthologue in Caenorhabditis elegans (mdt-28) and showed that it is involved in a spectrum of developmental processes. Here, we studied the proteomic interactome of MDT-28 edited as GFP::MDT-28 using Crispr/Cas9 technology or MDT-28::GFP expressed from extrachromosomal arrays in transgenic C. elegans exploiting the GFPTRAP system and mass spectrometry. The results show that MDT-28 associates with the Head module subunits MDT-6, MDT-8, MDT-11, MDT-17, MDT- 20, MDT-22, and MDT-30 and the Middle module subunit MDT-14. The analyses also identified additional proteins as preferential MDT-28 interactants, including chromatin-organizing proteins, structural proteins and enzymes. The results provide evidence for MDT-28 engagement in the Mediator Head module and support the possibility of physical (direct or indirect) interaction of MDT-28 with additional proteins, reflecting the transcription-regulating potential of primarily structural and enzymatic proteins at the level of the Mediator complex.

• MeSH
• alely MeSH
• Caenorhabditis elegans metabolismus   MeSH
• jaderné proteiny metabolismus   MeSH
• mediátorový komplex metabolismus   MeSH
• podjednotky proteinů metabolismus   MeSH
• proteiny Caenorhabditis elegans metabolismus   MeSH
• proteomika * MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• jaderné proteiny MeSH
• MDT-28 protein, C elegans MeSH Prohlížeč
• mediátorový komplex MeSH
• podjednotky proteinů MeSH
• proteiny Caenorhabditis elegans MeSH

Mediator is a multiprotein complex that connects regulation mediated by transcription factors with RNA polymerase II transcriptional machinery and integrates signals from the cell regulatory cascades with gene expression. One of the Mediator subunits, Mediator complex subunit 28 (MED28), has a dual nuclear and cytoplasmic localization and function. In the nucleus, MED28 functions as part of Mediator and in the cytoplasm, it interacts with cytoskeletal proteins and is part of the regulatory cascades including that of Grb2. MED28 thus has the potential to bring cytoplasmic regulatory interactions towards the centre of gene expression regulation. In this study, we identified MDT-28, the nematode orthologue of MED28, as a likely target of lysine acetylation using bioinformatic prediction of posttranslational modifications. Lysine acetylation was experimentally confirmed using anti-acetyl lysine antibody on immunoprecipitated GFP::MDT-28 expressed in synchronized C. elegans. Valproic acid (VPA), a known inhibitor of lysine deacetylases, enhanced the lysine acetylation of GFP::MDT-28. At the subcellular level, VPA decreased the nuclear localization of GFP::MDT-28 detected by fluorescencelifetime imaging microscopy (FLIM). This indicates that the nuclear pool of MDT-28 is regulated by a mechanism sensitive to VPA and provides an indirect support for a variable relative proportion of MED28 orthologues with other Mediator subunits.

• MeSH
• acetylace MeSH
• buněčné jádro účinky léků   metabolismus   MeSH
• Caenorhabditis elegans účinky léků   metabolismus   MeSH
• denzitometrie MeSH
• jaderné proteiny chemie   metabolismus   MeSH
• kyselina valproová farmakologie   MeSH
• larva účinky léků   MeSH
• lidé MeSH
• lysin metabolismus   MeSH
• mediátorový komplex chemie   metabolismus   MeSH
• proteiny Caenorhabditis elegans chemie   metabolismus   MeSH
• rekombinantní fúzní proteiny metabolismus   MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin * MeSH
• transport proteinů účinky léků   MeSH
• výpočetní biologie MeSH
• zelené fluorescenční proteiny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• jaderné proteiny MeSH
• kyselina valproová MeSH
• lysin MeSH
• MDT-28 protein, C elegans MeSH Prohlížeč
• mediátorový komplex MeSH
• proteiny Caenorhabditis elegans MeSH
• rekombinantní fúzní proteiny MeSH
• zelené fluorescenční proteiny MeSH

Lens epithelium-derived growth factor/p75 (LEDGF/p75, or PSIP1) is a transcriptional coactivator that tethers other proteins to gene bodies. The chromatin tethering function of LEDGF/p75 is hijacked by HIV integrase to ensure viral integration at sites of active transcription. LEDGF/p75 is also important for the development of mixed-lineage leukemia (MLL), where it tethers the MLL1 fusion complex at aberrant MLL targets, inducing malignant transformation. However, little is known about how the LEDGF/p75 protein interaction network is regulated. Here, we obtained solution structures of the complete interfaces between the LEDGF/p75 integrase binding domain (IBD) and its cellular binding partners and validated another binding partner, Mediator subunit 1 (MED1). We reveal that structurally conserved IBD-binding motifs (IBMs) on known LEDGF/p75 binding partners can be regulated by phosphorylation, permitting switching between low- and high-affinity states. Finally, we show that elimination of IBM phosphorylation sites on MLL1 disrupts the oncogenic potential of primary MLL1-rearranged leukemic cells. Our results demonstrate that kinase-dependent phosphorylation of MLL1 represents a previously unknown oncogenic dependency that may be harnessed in the treatment of MLL-rearranged leukemia.

• Klíčová slova
• LEDGF/p75, disordered proteins, leukemia, phosphorylation, protein–protein interactions,
• MeSH
• adaptorové proteiny signální transdukční genetika   metabolismus   MeSH
• aminokyselinové motivy MeSH
• fosforylace genetika   MeSH
• histonlysin-N-methyltransferasa genetika   metabolismus   MeSH
• HIV-integrasa genetika   metabolismus   MeSH
• HIV enzymologie   genetika   MeSH
• lidé MeSH
• mediátorový komplex - podjednotka 1 genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• protoonkogenní protein MLL genetika   metabolismus   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• histonlysin-N-methyltransferasa MeSH
• HIV-integrasa MeSH
• KMT2A protein, human MeSH Prohlížeč
• MED1 protein, human MeSH Prohlížeč
• mediátorový komplex - podjednotka 1 MeSH
• protoonkogenní protein MLL MeSH
• PSIP1 protein, human MeSH Prohlížeč
• transkripční faktory MeSH

The clinical significance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remains largely unexplored. Here, we analyzed a large panel of lncRNA candidates with The Cancer Genome Atlas (TCGA) CRC dataset, and identified H19 as the most significant lncRNA associated with CRC patient survival. We further validated such association in two independent CRC cohorts. H19 silencing blocked G1-S transition, reduced cell proliferation, and inhibited cell migration. We profiled gene expression changes to gain mechanism insight of H19 function. Transcriptome data analysis revealed not only previously identified mechanisms such as Let-7 regulation by H19, but also RB1-E2F1 function and β-catenin activity as essential upstream regulators mediating H19 function. Our experimental data showed that H19 affects phosphorylation of RB1 protein by regulating gene expression of CDK4 and CCND1. We further demonstrated that reduced CDK8 expression underlies changes of β-catenin activity, and identified that H19 interacts with macroH2A, an essential regulator of CDK8 gene transcription. However, the relevance of H19-macroH2A interaction in CDK8 regulation remains to be experimentally determined. We further explored the clinical relevance of above mechanisms in clinical samples, and showed that combined analysis of H19 with its targets improved prognostic value of H19 in CRC.

• Klíčová slova
• CDK8, Colorectal cancer, E2F, H19, RB1, β-Catenin,
• MeSH
• analýza přežití MeSH
• beta-katenin metabolismus   MeSH
• cyklin-dependentní kinasa 8 genetika   metabolismus   MeSH
• databáze nukleových kyselin MeSH
• genové regulační sítě MeSH
• kolorektální nádory genetika   metabolismus   mortalita   patologie   MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• prognóza MeSH
• regulace genové exprese u nádorů MeSH
• retinoblastomový protein metabolismus   MeSH
• RNA dlouhá nekódující genetika   MeSH
• RNA interference MeSH
• signální transdukce * MeSH
• stanovení celkové genové exprese MeSH
• transkripční faktory E2F metabolismus   MeSH
• transkriptom MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-katenin MeSH
• cyklin-dependentní kinasa 8 MeSH
• H19 long non-coding RNA MeSH Prohlížeč
• retinoblastomový protein MeSH
• RNA dlouhá nekódující MeSH
• transkripční faktory E2F MeSH