Chromatinlandschaften prägende Monarchien und Hierarchien

  • Decker, Thomas (Co-Projektleiter*in)
  • Müller, Mathias (Projektleiter*in)
  • Bock, Christoph (Co-Projektleiter*in)
  • Knapp, Sylvia (Co-Projektleiter*in)
  • Moriggl, Richard (Co-Projektleiter*in)
  • Sexl, Veronika (Co-Projektleiter*in)
  • Strobl, Birgit (Co-Projektleiter*in)
  • Dolezal, Marlies (Co-Projektleiter*in)
  • Endler, Lukas (Co-Projektleiter*in)
  • Farlik, Matthias (Co-Projektleiter*in)
  • Grausenburger, Reinhard (Co-Projektleiter*in)
  • Halbritte, Johannes (Co-Projektleiter*in)
  • Hölbl-Kovacic, Andrea (Co-Projektleiter*in)
  • Kolbe, Thomas (Co-Projektleiter*in)
  • Lassnig, Caroline (Co-Projektleiter*in)
  • Macho-Maschler, Sabine (Co-Projektleiter*in)
  • Meissl, Katrin (Co-Projektleiter*in)
  • Menche, Jörg (Co-Projektleiter*in)
  • Platanitis, Ekaterini (Co-Projektleiter*in)
  • Prchal-Murphy, Michaela (Co-Projektleiter*in)
  • Schlötterer, Christian (Co-Projektleiter*in)
  • Tschismarov, Roland Alexander (Co-Projektleiter*in)
  • Vogl, Claus (Co-Projektleiter*in)

Projekt: Forschungsförderung

Projektdetails

Abstract

Infection causes drastic transcriptome shifts towards antimicrobial gene signatures. We will examine the transcriptional response of bone marrow macrophages to infection with the intracellular bacterium Listeria monocytogenes, with a specific focus on changes to diagnostic chromatin modifications, DNA accessibility and intra- as well as interchromosomal interactions. Our work will concentrate on two important groups of genes within the antimicrobial transcriptome: classical type I interferon (IFN-I)-induced genes (ISGs), regulated by the ISGF3 (STAT1/STAT2/IRF9) complex, and a previously described group of ‘synergy genes’, defined by a two-signal activation that depends on cooperativity between the IFN-I/ISGF3 and NFκB pathways. We will examine differences in chromatin landscapes before and following infection. Particular efforts will be made to test the hypothesis that the need for diverse regulatory input to ISGs and ‘synergy genes’ derives from functional assignment to different chromosomal topologically associated domains (TAD), defined by insulation and/or by tertiary structure. Finally, we will apply genome editing to validate the functional relevance of enhancers regulating ISG and synergy genes and to disrupt TAD insulation. We will interconvert enhancers between the two gene groups and test the effect on gene regulation and 3D structure. Our long-term goal is to generate a comprehensive view of the importance of genome structure and chromatin landscapes in co-regulating groups of genes during microbial infection.
StatusAbgeschlossen
Tatsächlicher Beginn/ -es Ende1/03/1728/02/21

Projektbeteiligte

  • Universität Wien
  • Österreichische Akademie der Wissenschaften (ÖAW)
  • Veterinärmedizinische Universität Wien (Leitung)
  • Medizinische Universität Wien

Schlagwörter

  • JAK-StAT signalling
  • Hematopoietic malignancies
  • Transcriptional activation and epigenetics
  • Immunity to infection
  • Next generation sequencing Technologies
  • Mouse genetic engineering