Group Leader

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Dr. Asifa Akhtar
Senior Group Leader and Managing Director
Phone:+49 761 5108 565

Lab Asifa Akhtar

Assistant: Linda Schmidl phone: +49 761 5108 564 Email: schmidl@ie-freiburg.mpg.de

Laboratory Asifa Akhtar

Function of the mammalian MSL and NSL complexes

There is a remarkable evolutionary conservation of the Drosophila and mammalian MSL and NSL complexes at the biochemical level, implying a functional role for these proteins in gene regulation. Interestingly, loss of MOF leads to early embryonic lethality indicating that this protein is essential during mouse development. Furthermore, MOF and H4K16ac are frequently mis-regulated in cancer suggesting that it is critical for cellular homeostasis of mammalian cells to maintain appropriate levels this histone modification. We are interested in exploring what aspect of MOF mediated regulation is conserved in mammals and how is the division of labor between the MSL and the NSL complexes achieved in mammalian cells. We have identified an interesting evolutionary link between the fly and mammalian MSL complexes in X chromosomal regulation.

In male Drosophilas, the gene expression of the single X Chromosome is upregulated to get equal levels with female individuals. Zoom Image
In male Drosophilas, the gene expression of the single X Chromosome is upregulated to get equal levels with female individuals. [less]
In female mammals, one of the two X chromosomes is silenced. The MSL homologue, however, seems to play an important role in embryonic development and cancer. Zoom Image
In female mammals, one of the two X chromosomes is silenced. The MSL homologue, however, seems to play an important role in embryonic development and cancer. [less]

By targeting an enhancer which regulates Tsix, an antisense transcript controlling the expression of Xist long-non-coding RNA, the MSL complex members ensure that the X chromosome remains active in embryonic stem cells. In future, we plan to explore further the mechanism by which MSL proteins play a role during X chromosome inactivation in mammals.

Our recent work has also revealed that the mammalian MSL and NSL complexes are not only major regulators of housekeeping gene function but are also involved in tissue specific regulation by targeting a variety of enhancers in mammals. Moreover, cellular function of NSL proteins extends beyond their epigenetic role during interphase. We have shown that mammalian KANSL1 and KANSL3 proteins decorate the mitotic spindle and have identified KANSL3 as a novel microtubule minus end binding protein. Thus, our work revealed novel functions of NSL complex members during different stages of cell cycle. In future we plan explore how interphase versus mitotic functions are coordinated by NSL complex members in mammals.

<strong>Fig 2:</strong> KANSL proteins, how NSL proteins are called in mammals, localize to the poles of the mitotic spinde. <br /><br /><strong>Left </strong><span><strong>panel:</strong> Immuno</span><span>fl</span><span>uorescence of the mitotic spindle. KANSL3 is shown in green, tubulin in red and DNA in blue. Overlaps between red and green appears as yellow. <br /><br /><strong>Right Panel:</strong> Schematic representation of KANSL proteins on the mitotic spindle (upper half) and microbules. </span> Zoom Image
Fig 2: KANSL proteins, how NSL proteins are called in mammals, localize to the poles of the mitotic spinde.

Left panel: Immunofluorescence of the mitotic spindle. KANSL3 is shown in green, tubulin in red and DNA in blue. Overlaps between red and green appears as yellow.

Right Panel: Schematic representation of KANSL proteins on the mitotic spindle (upper half) and microbules. 
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