kth.sePublications
Change search
Refine search result
1 - 7 of 7
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    de Thonel, Aurelie
    et al.
    Univ Paris, CNRS, Epigenet & Cell Fate, F-75013 Paris, France..
    Vihervaara, Anniina
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. Abo Akad Univ, Fac Sci & Engn, Cell Biol, Turku, Finland.;Univ Turku, Turku Biosci Ctr, Turku, Finland..
    Mezger, Valerie
    Univ Paris, CNRS, Epigenet & Cell Fate, F-75013 Paris, France..
    et al.,
    CBP-HSF2 structural and functional interplay in Rubinstein-Taybi neurodevelopmental disorder2022In: Nature Communications, E-ISSN 2041-1723, Vol. 13, no 1, article id 7002Article in journal (Refereed)
    Abstract [en]

    Rubinstein-Taybi syndrome (RSTS) is a neurodevelopmental disorder with unclear underlying mechanisms. Here, the authors unravel the contribution of a stress-responsive pathway to RSTS where impaired HSF2 acetylation, due to RSTS-associated CBP/EP300 mutations, alters the expression of neurodevelopmental players, in keeping with hallmarks of cell-cell adhesion defects. Patients carrying autosomal dominant mutations in the histone/lysine acetyl transferases CBP or EP300 develop a neurodevelopmental disorder: Rubinstein-Taybi syndrome (RSTS). The biological pathways underlying these neurodevelopmental defects remain elusive. Here, we unravel the contribution of a stress-responsive pathway to RSTS. We characterize the structural and functional interaction between CBP/EP300 and heat-shock factor 2 (HSF2), a tuner of brain cortical development and major player in prenatal stress responses in the neocortex: CBP/EP300 acetylates HSF2, leading to the stabilization of the HSF2 protein. Consequently, RSTS patient-derived primary cells show decreased levels of HSF2 and HSF2-dependent alteration in their repertoire of molecular chaperones and stress response. Moreover, we unravel a CBP/EP300-HSF2-N-cadherin cascade that is also active in neurodevelopmental contexts, and show that its deregulation disturbs neuroepithelial integrity in 2D and 3D organoid models of cerebral development, generated from RSTS patient-derived iPSC cells, providing a molecular reading key for this complex pathology.

  • 2.
    Delemotte, Lucie
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Garcia, Sarahi L.
    Stockholm Univ, Dept Ecol Environm & Plant Sci, Sci Life Lab, S-10691 Stockholm, Sweden..
    Rodriguez-Gijon, Alejandro
    Stockholm Univ, Dept Ecol Environm & Plant Sci, Sci Life Lab, S-10691 Stockholm, Sweden..
    Sezgin, Erdinc
    Karolinska Inst, Dept Womens & Childrens Hlth, Sci Life Lab, S-17165 Solna, Sweden..
    Vihervaara, Anniina
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uniting diversity to create a more inclusive academic environment2022In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 135, no 7, article id jcs259977Article in journal (Refereed)
  • 3. Himanen, S. V.
    et al.
    Puustinen, M. C.
    Da Silva, A. J.
    Vihervaara, Anniina
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sistonen, L.
    HSFs drive transcription of distinct genes and enhancers during oxidative stress and heat shock2022In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 50, no 11, p. 6102-6115Article in journal (Refereed)
    Abstract [en]

    Reprogramming of transcription is critical for the survival under cellular stress. Heat shock has provided an excellent model to investigate nascent transcription in stressed cells, but the molecular mechanisms orchestrating RNA synthesis during other types of stress are unknown. We utilized PRO-seq and ChIP-seq to study how Heat Shock Factors, HSF1 and HSF2, coordinate transcription at genes and enhancers upon oxidative stress and heat shock. We show that pause-release of RNA polymerase II (Pol II) is a universal mechanism regulating gene transcription in stressed cells, while enhancers are activated at the level of Pol II recruitment. Moreover, besides functioning as conventional promoter-binding transcription factors, HSF1 and HSF2 bind to stress-induced enhancers to trigger Pol II pause-release from poised gene promoters. Importantly, HSFs act at distinct genes and enhancers in a stress type-specific manner. HSF1 binds to many chaperone genes upon oxidative and heat stress but activates them only in heat-shocked cells. Under oxidative stress, HSF1 localizes to a unique set of promoters and enhancers to trans-activate oxidative stress-specific genes. Taken together, we show that HSFs function as multi-stress-responsive factors that activate distinct genes and enhancers when encountering changes in temperature and redox state. 

  • 4.
    Vihervaara, Anniina
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Abo Akad Univ, Fac Sci & Engn, Cell Biol, Turku 20520, Finland.;Univ Turku, Turku Biosci Ctr, Turku 20520, Finland.;Abo Akad Univ, Turku 20520, Finland.;Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA..
    Mahat, Dig Bijay
    Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA.;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Himanen, Samu, V
    Abo Akad Univ, Fac Sci & Engn, Cell Biol, Turku 20520, Finland.;Univ Turku, Turku Biosci Ctr, Turku 20520, Finland.;Abo Akad Univ, Turku 20520, Finland..
    Blom, Malin A. H.
    Abo Akad Univ, Fac Sci & Engn, Cell Biol, Turku 20520, Finland.;Univ Turku, Turku Biosci Ctr, Turku 20520, Finland.;Abo Akad Univ, Turku 20520, Finland..
    Lis, John T.
    Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA..
    Sistonen, Lea
    Abo Akad Univ, Fac Sci & Engn, Cell Biol, Turku 20520, Finland.;Univ Turku, Turku Biosci Ctr, Turku 20520, Finland.;Abo Akad Univ, Turku 20520, Finland..
    Stress-induced transcriptional memory accelerates promoter-proximal pause release and decelerates termination over mitotic divisions2021In: Molecular Cell, ISSN 1097-2765, E-ISSN 1097-4164, Vol. 81, no 8, p. 1715-+Article in journal (Refereed)
    Abstract [en]

    Heat shock instantly reprograms transcription. Whether gene and enhancer transcription fully recover from stress and whether stress establishes a memory by provoking transcription regulation that persists through mitosis remained unknown. Here, we measured nascent transcription and chromatin accessibility in unconditioned cells and in the daughters of stress-exposed cells. Tracking transcription genome-wide at nucleotide-resolution revealed that cells precisely restored RNA polymerase II (Pol II) distribution at gene bodies and enhancers upon recovery from stress. However, a single heat exposure in embryonic fibroblasts primed a faster gene induction in their daughter cells by increasing promoter-proximal Pol II pausing and by accelerating the pause release. In K562 erythroleukemia cells, repeated stress refined basal and heat-induced transcription over mitotic division and decelerated termination-coupled pre-mRNA processing. The slower termination retained transcripts on the chromatin and reduced recycling of Pol II. These results demonstrate that heat-induced transcriptional memory acts through promoter-proximal pause release and pre-mRNA processing at transcription termination.

  • 5.
    Vihervaara, Anniina
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sistonen, Lea
    Abo Akad Univ, Cell & Mol Biol, Turku, Finland.;Turku Biosci Ctr, Turku, Finland..
    Meet the authors: Anniina Vihervaara and Lea Sistonen2021In: Molecular Cell, ISSN 1097-2765, E-ISSN 1097-4164, Vol. 81, no 8, p. 1588-1590Article in journal (Other academic)
  • 6.
    Vihervaara, Anniina
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, 14853, USA.
    Versluis, Philip
    Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, 14853, USA.
    Himanen, Samu V.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lis, John T.
    Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, 14853, USA.
    PRO-IP-seq tracks molecular modifications of engaged Pol II complexes at nucleotide resolution2023In: Nature Communications, E-ISSN 2041-1723, Vol. 14, no 1, article id 7039Article in journal (Refereed)
    Abstract [en]

    RNA Polymerase II (Pol II) is a multi-subunit complex that undergoes covalent modifications as transcription proceeds through genes and enhancers. Rate-limiting steps of transcription control Pol II recruitment, site and degree of initiation, pausing duration, productive elongation, nascent transcript processing, transcription termination, and Pol II recycling. Here, we develop Precision Run-On coupled to Immuno-Precipitation sequencing (PRO-IP-seq), which double-selects nascent RNAs and transcription complexes, and track phosphorylation of Pol II C-terminal domain (CTD) at nucleotide-resolution. We uncover precise positional control of Pol II CTD phosphorylation as transcription proceeds from the initiating nucleotide (+1 nt), through early (+18 to +30 nt) and late (+31 to +60 nt) promoter-proximal pause, and into productive elongation. Pol II CTD is predominantly unphosphorylated from initiation until the early pause-region, whereas serine-2- and serine-5-phosphorylations are preferentially deposited in the later pause-region. Upon pause-release, serine-7-phosphorylation rapidly increases and dominates over the region where Pol II assembles elongation factors and accelerates to its full elongational speed. Interestingly, tracking CTD modifications upon heat-induced transcriptional reprogramming demonstrates that Pol II with phosphorylated CTD remains paused on thousands of heat-repressed genes. These results uncover dynamic Pol II regulation at rate-limiting steps of transcription and provide a nucleotide-resolution technique for tracking composition of engaged transcription complexes.

  • 7.
    Wang, Zhijia
    et al.
    Department of Biochemistry and Developmental Biology, University of Helsinki, Helsinki FIN-00014, Finland.
    Himanen, Samu V.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Haikala, Heidi M.
    Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki FIN-00014, Finland; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki FIN-00014, Finland.
    Friedel, Caroline C.
    Institute of Informatics, Ludwig-Maximilians-Universität München, 80333 Munich, Germany.
    Vihervaara, Anniina
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Barborič, Matjaž
    Department of Biochemistry and Developmental Biology, University of Helsinki, Helsinki FIN-00014, Finland.
    Inhibition of CDK12 elevates cancer cell dependence on P-TEFb by stimulation of RNA polymerase II pause release2023In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 51, no 20, p. 10970-10991Article in journal (Refereed)
    Abstract [en]

    P-TEFb and CDK12 facilitate transcriptional elongation by RNA polymerase II. Given the prominence of both kinases in cancer, gaining a better understanding of their interplay could inform the design of novel anti-cancer strategies. While down-regulation of DNA repair genes in CDK12-targeted cancer cells is being explored therapeutically, little is known about mechanisms and significance of transcriptional induction upon inhibition of CDK12. We show that selective targeting of CDK12 in colon cancer-derived cells activates P-TEFb via its release from the inhibitory 7SK snRNP. In turn, P-TEFb stimulates Pol II pause release at thousands of genes, most of which become newly dependent on P-TEFb. Amongst the induced genes are those stimulated by hallmark pathways in cancer, including p53 and NF-κB. Consequently, CDK12-inhibited cancer cells exhibit hypersensitivity to inhibitors of P-TEFb. While blocking P-TEFb triggers their apoptosis in a p53-dependent manner, it impedes cell proliferation irrespective of p53 by preventing induction of genes downstream of the DNA damage-induced NF-κB signaling. In summary, stimulation of Pol II pause release at the signal-responsive genes underlies the functional dependence of CDK12-inhibited cancer cells on P-TEFb. Our study establishes the mechanistic underpinning for combinatorial targeting of CDK12 with either P-TEFb or the induced oncogenic pathways in cancer.

1 - 7 of 7
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf