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  • Z01
    • Backofen
    • Manke
  • Z02
    • Breit
    • Einsle
    • Günther
  • Z03 Central tasks

A02 The role of histone acetyltransferase MOF in development and disease

Asifa Akhtar

Asifa Akhtar

Principal investigator of

The male specific lethal (MSL) complex is an evolutionarily conserved complex in Drosophila and mammals that contains the histone acetyltransferase MOF. This project aims to study the dynamics of the MSL complex during development using live imaging in early mouse embryos and plans to perform biochemical purifications in undifferentiated and differentiated cells with the aim to identify cell-type specific interaction partners of MSL proteins. Combining biochemical, genomic and in vivo analyses promises to reveal novel mechanistic insights into the evolutionary conserved function of the MSL complex in mammals.

Selected project-relevant publications

  • Ilik I.A., Maticzka D., Georgiev P., Gutierrez N.M., Backofen R. and Akhtar A. (2017) A mutually exclusive stem-loop arrangement in roX2 RNA is essential for X-chromosome regulation in Drosophila. Genes Dev 31, 1973-1987.
  • Aktas T., Avsar Ilik I., Maticzka D., Bhardwaj V., Pessoa Rodrigues C., Mittler G., Manke T., Backofen R. and Akhtar A. (2017) DHX9 suppresses RNA processing defects originating from the Alu invasion of the human genome. Nature 544, 115-119.
  • Chatterjee A., Seyfferth J., Lucci J., Gilsbach R., Preissl S., Bottinger L., Martensson C.U., Panhale A., Stehle T., Kretz O., Sahyoun A.H., Avilov S., Eimer S., Hein L., Pfanner N., Becker T. and Akhtar A. (2016) MOF Acetyl Transferase Regulates Transcription and Respiration in Mitochondria. Cell 167, 722-738.e723.
  • Chlamydas S., Holz H., Samata M., Chelmicki T., Georgiev P., Pelechano V., Dundar F., Dasmeh P., Mittler G., Cadete F.T., Ramirez F., Conrad T., Wei W., Raja S., Manke T., Luscombe N.M., Steinmetz L.M. and Akhtar A. (2016) Functional interplay between MSL1 and CDK7 controls RNA polymerase II Ser5 phosphorylation. Nat Struct Mol Biol 23, 580-589.
  • Quinn J.J., Zhang Q.C., Georgiev P., Ilik I.A., Akhtar A. and Chang H.Y. (2016) Rapid evolutionary turnover underlies conserved lncRNA-genome interactions. Genes Dev 30, 191-207.
  • Sheikh B.N., Bechtel-Walz W., Lucci J., Karpiuk O., Hild I., Hartleben B., Vornweg J., Helmstadter M., Sahyoun A.H., Bhardwaj V., Stehle T., Diehl S., Kretz O., Voss A.K., Thomas T., Manke T., Huber T.B. and Akhtar A. (2016) MOF maintains transcriptional programs regulating cellular stress response. Oncogene 35, 2698-2710.
  • Ramirez F., Lingg T., Toscano S., Lam K.C., Georgiev P., Chung H.R., Lajoie B.R., De Wit E., Zhan Y., De Laat W., Dekker J., Manke T. and Akhtar A. (2015) High-Affinity Sites Form an Interaction Network to Facilitate Spreading of the MSL Complex across the X Chromosome in Drosophila. Mol Cell 60, 146-162.
  • Meunier S., Shvedunova M., Van Nguyen N., Avila L., Vernos I. and Akhtar A. (2015) An epigenetic regulator emerges as microtubule minus-end binding and stabilizing factor in mitosis. Nat Commun 6, 7889.
  • Quinn J.J., Ilik I.A., Qu K., Georgiev P., Chu C., Akhtar A. and Chang H.Y. (2014) Revealing long noncoding RNA architecture and functions using domain-specific chromatin isolation by RNA purification. Nat Biotechnol 32, 933-940.
  • Dias J., Van Nguyen N., Georgiev P., Gaub A., Brettschneider J., Cusack S., Kadlec J. and Akhtar A. (2014) Structural analysis of the KANSL1/WDR5/KANSL2 complex reveals that WDR5 is required for efficient assembly and chromatin targeting of the NSL complex. Genes Dev 28, 929-942.
  • Ilik I.A., Quinn J.J., Georgiev P., Tavares-Cadete F., Maticzka D., Toscano S., Wan Y., Spitale R.C., Luscombe N., Backofen R., Chang H.Y. and Akhtar A. (2013) Tandem stem-loops in roX RNAs act together to mediate X chromosome dosage compensation in Drosophila. Mol Cell 51, 156-173.
  • Conrad T., Cavalli F.M., Vaquerizas J.M., Luscombe N.M. and Akhtar A. (2012) Drosophila dosage compensation involves enhanced Pol II recruitment to male X-linked promoters. Science 337, 742-746.