Funktionelle Analyse der neuen H2A.Z Chaperon/Remodeling Komplexmitglieder MBTD1 und JAZF1

• Antragstellerin: Professorin Dr. Sandra Brigitte Hake
• Fachliche Zuordnung: Allgemeine Genetik und funktionelle Genomforschung ; Biochemie
• Förderung: Förderung von 2015 bis 2020
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 269853135

• Erstellungsjahr: 2021

Zusammenfassung der Projektergebnisse

Histone variants differ in amino acid sequence, expression timing and genomic localization sites from their canonical counter parts and convey unique functions to eukaryotic cells. Their tightly controlled spatial and temporal deposition into specific chromatin regions is accomplished by dedicated chaperone and/or remodeling complexes. While quantitatively identifying the chaperone complexes of many human H2A variants by using mass spectrometry, we also found additional members of the known H2A.Z chaperone complexes p400/TIP60/NuA4 and SCARP. We discovered JAZF1, a nuclear/nucleolar protein, as a member of a p400 sub-complex containing MBTD1 but excluding ANP32E. Depletion of JAZF1 results in transcriptome changes that affect, among other pathways, ribosome biogenesis, as we could also demonstrate by increases in nucleoli sizes. To identify the underlying molecular mechanism contributing to JAZF1’s function in gene regulation, we performed genome-wide ChIP-seq analyses. Interestingly, depletion of JAZF1 leads to reduced H2A.Z acetylation levels at > 1.000 regulatory sites without affecting H2A.Z nucleosome positioning. Since JAZF1 associates with the histone acetyltransferase TIP60, whose depletion causes a correlated H2A.Z deacetylation at several JAZF1-targeted enhancer regions, we speculate that JAZF1 acts as a member of a TIP60- containing p400 chaperone complex orchestrating H2A.Z acetylation at regulatory regions controlling the expression of genes, many of which are involved in ribosome biogenesis.

Projektbezogene Publikationen (Auswahl)

• (2021). JAZF1, a novel p400/TIP60/NuA4 complex member, regulates H2A.Z acetylation at regulatory regions. Int J Mol Sci. 22(2): 678
  Procida T., Friedrich T., Jack A.P.M., Peritore M., Bönisch C., Eberl H.C., Daus N., Kletenkov K., Nist A., Stiewe T., Borggrefe T., Mann M., Bartkuhn M. and Hake S.B.
  (Siehe online unter https://doi.org/10.3390/ijms22020678)