A06 The role of epigenetic regulators MOF and KANSL1 in kidney homeostasis

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27

  • B01
    • Walz
    • Kammerer
  • B02
    • Köttgen
  • B04
    • Bergmann
  • B06
    • Schmidts
    • Lausch
  • B07
    • Lienkamp
    • Arnold

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29

  • Z01
    • Nitschke
    • Eimer
  • Z02
    • Brox
    • Ronneberger
Asifa Akhtar

Asifa Akhtar

Principal investigator of

It is becoming increasingly clear that epigenetic regulation plays an important role in development and disease. Our longstanding interest is to study the epigenetic phenomenon of dosage compensation of the X chromosome. However, our recent work has identified a new chromatin modifying non-specific lethal (NSL) complex that is a major transcriptional regulator in the Drosophila genome for X chromosomal as well as autosomal genes. The NSL complex is conserved in mammals and contains seven different components (NSL1 (KANSL1), NSL2 (KANSL2), NSL3 (KANSL3), MCRS1, PHF20, WDR5 and histone acetyl transferase MOF). Interestingly, haploinsufficiency of KANSL1, a core component of this complex, has recently been shown to be associated with the 17q21.31 microdeletion syndrome, a novel genomic disorder in humans. The affected individuals not only suffer from developmental delay and facial dysmorphism but among the clinically important features also include heart defects and kidney anomalies. Thus 17q21.31 microdeletion syndrome clearly associates a defective activity of the MOF-containing NSL complex with developmental defects, notably during kidney and urinary tract formation. Additional lines of evidence show that MOF is frequently misregulated in several types of cancers including renal cell carcinoma, suggesting that the NSL complex might be as well required for proper maintenance of kidney homeostasis after development. In this proposal, we plan to perform thorough physiological and biochemical analyses of KANSL1 and MOF focussing on renal tissue.