Laboratory Asifa Akhtar

Laboratory Asifa Akhtar

DNA tightly packed together with histones into nucleosomes is not easily accessible to the enzymes that use it as a template for transcription or replication. Consequently, remodelling of chromatin structure may play an essential role in the regulation of gene expression. Structural changes in chromatin may also form the basis for dosage compensation mechanisms that have evolved to equalise levels of X-linked gene products between males and females. In humans, one of the two X chromosomes in females is randomly inactivated by condensation of the chromosome into a Barr body, a process known as X-inactivation. In contrast, in Drosophila this is achieved by a two fold hyper-transcription of the genes on the male X chromosome. Genetic studies have identified a number of factors that are important for dosage compensation in Drosophila, including five proteins [MSL1, MSL2, MSL3, MLE, MOF] and two non-coding RNAs [roX1 and roX2]. The hyperactive X is also specifically hyper-acetylated at histone H4, acetylation which is achieved by the MOF histone acetyl transferase.

Our major goal is to study the epigenetic mechanisms underlying X-chromosome specific gene regulation using Drosophila dosage compensation as a model system. More specifically, we are interested in addressing how the dosage compensation complex, composed of RNA and proteins [the MSL complex], gets targeted to the X chromosome. In addition, we are studying the mechanism by which the MSL complex modulates X chromosomal transcriptional output.

Senior Group Leader

Asifa Akhtar
phone: -565

akhtar@immunbio.mpg.de

1971
Born in Karachi, Pakistan, Undergraduate studies in Biology at University College London, UK

1994-1997
PhD studies at Imperial Cancer Research Fund, London, UK

1998-2001
Postdoctoral fellow at EMBL, Heidelberg and the Adolf-Butenandt-Institut, Munich, Germany

2001 - 2009
Group Leader at EMBL, Heidelberg, Germany

Since 2009
Head of the Laboratory of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

Project Areas

The role of non-coding RNA in dosage-compensation

The involvement of non-coding RNAs as potential targeting molecules adds another level of complexity to chromatin regulation. Interestingly, the dosage...

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The role of the nuclear periphery in X chromosomal regulation

We have recently discovered the involvement of nuclear pore components in the regulation of dosage compensation in Drosophila. This work has raised several...

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The role of the NSL complex in gene regulation

We have recently biochemically purified a novel NSL complex that is associated with MOF histone acetyltransferase in Drosophila and mammals. Members of this...

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The function of the mammalian MSL complex

There is a remarkable evolutionary conservation of all the known Drosophila dosage compensation complex members in mammals. In fact, we have recently purified...

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Recent Publications

The MOF Chromobarrel Domain Controls Genome-wide H4K16 Acetylation and Spreading of the MSL Complex
Conrad, T., Cavalli, F.M.G., Holz, H.,Hallacli, E., Kind, J., Ilik, I., Vaquerizas, J.M., Luscombe, N.M., Akhtar A. (2012)
Dev. Cell 22, 610-624
Dosage compensation in Drosophila melanogaster: epigenetic fine-tuning of chromosome-wide transcription
Akhtar, A., Conrad, T. (2012)
Nature Reviews Genetics 13, 123-134 , Epub 18.01.2012
A decade of molecular cell biology: achievements and challenges.
Akhtar, A., Fuchs, E., Mitchison, T., Shaw, RJ., St Johnston, D., Strasser, A., Taylor, S., Walczak, C., Zerial, M. (2011)
Nat Rev Mol Cell Biol. 12, 669-674
Drosophila dosage compensation: Males are from Mars, females are from Venus.
Georgiev, P., Chlamydas, S., Akhtar, A. (2011)
Fly (Austin) 5, 147-154
Multiple facets of nuclear periphery in gene expression control.
Arib, G., Akhtar, A. (2011)
Curr Opin Cell Biol. 23, 346-353
Structural basis for MOF and MSL3 recruitment into the dosage compensation complex by MSL1.
Kadlec, J., Hallacli, E., Lipp, M., Holz, H., Sanchez-Weatherby, J., Cusack, S., Akhtar, A. (2011)
Nat Struct Mol Biol. 18, 142-149
NSL complex is a novel transcription regulator in Drosophila.
Raja, S.J., Charapitsa, I., Conrad, T., Vaquerizas, J.M. Gebhardt, P., Holz, H., Fraterman, S., Luscombe, N.M. and Akhtar, A. (2010)
Molecular Cell 38, 827-841
Nuclear pore proteins nup153 and megator define transcriptionally active regions in the Drosophila genome.
Vaquerizas, J.M., Suyama, R., Kind, J., Miura, K., Luscombe, N.M. and Akhtar, A. (2010)
PLoS Genet. 6, e1000846
The MSL complex: X chromosome and beyond.
Laverty, C., Lucci, J. and Akhtar, A. (2010)
Curr Opin Genet Dev. 20, 171-178
X chromosomal regulation is flies: When less is more.
Hallacli, E. and Akhtar, A. (2009)
Chromosome Research 17, 603-619
Reversible acetylation of the chromatin remodeling complex NoRC is required for noncoding RNA-dependent transcriptional silencing.
Zhou, Y., Schmitz, K.-M., Mayer, C., Yuan, X., Akhtar, A. and Grummt, I. (2009)
Nature Cell Biology 11, 1010-1016
roX RNAs: Non-coding regulators of the male X chromosome in flies.
Ilik, I. and Akhtar, A. (2009)
RNA biology 6, 113-121
Genomewide analysis revealed MOF as key regulator of gene dosage compensation and gene expression in Drosophila.
Kind, J., Vaquerizas, J., Gebhardt, P., Gentzel, M., Luscombe, N.M., Bertone, P. and Akhtar, A. (2008)
Cell 133, 813-828
Transcription-coupled methylation of histone H3 at lysine 36 enhances recruitment of the MSL complex to the X chromosome in Drosophila
Bell, O., Conrad, T., Kind, J., Wirbelauer, C., Akhtar, A. and Schubeler, D. (2008)
Mol. and Cell. Biology 28, 3401-3409
The histone acetyltransferase hMOF is frequently downregulated in primary breast carcinoma and medulloblastoma and constitutes a biomarker for clinical outcome in medulloblastoma.
Pfister, S., Rea, S., Taipale, M., Mendrzyk, F., Straub, B., Ittrich, C., Thuerigen, O., Sinn, H.P., Akhtar, A. and Lichter, P. (2008)
Int. J. Cancer. 122, 1207-1213

Group Members

Group Leader

Akhtar, Asifa

phone: -565

akhtar@ie-freiburg.mpg.de
Administrative Assistant

Schmidl, Linda

phone: -564

schmidl@ie-freiburg.mpg.de
Postdoctoral Fellows

Arib, Ghislaine

phone: -693

arib@ie-freiburg.mpg.de
Chlamydas, Sarantis

phone: -707

chlamydas@ie-freiburg.mpg.de
Conrad, Thomas

phone: -691

conrad@ie-freiburg.mpg.de
Georgiev, Plamen

phone: -705

georgiev@ie-freiburg.mpg.de
Herquel, Benjamin

phone: -694

herquel@ie-freiburg.mpg.de
Ilik, Ibrahim Avsar

phone: -692

ilik@ie-freiburg.mpg.de
Khanam, Tasneem

phone: -704

khanam@ie-freiburg.mpg.de
Lempradl, Adelheid

phone: -691

lempradl@ie-freiburg.mpg.de
Toscano, Sarah

phone: -705

toscano@ie-freiburg.mpg.de
Ph.D. Students

Chatterjee, Aindrila

phone: -694

chatterjee@ie-freiburg.mpg.de
Chelmicki, Tomasz

phone: -694

chelmicki@ie-freiburg.mpg.de
Hallacli, Erinc

phone: -692

hallacli@ie-freiburg.mpg.de
Lam, Ken

phone: -514

lam@ie-freiburg.mpg.de
Lingg, Thomas

phone: -695

lingg@ie-freiburg.mpg.de
Lucci, Jacopo

phone: -693

lucci@ie-freiburg.mpg.de
Nguyen, Nhuong

phone: -706

nguyen@ie-freiburg.mpg.de
Panhale, Amol

phone: -706

panhale@ie-freiburg.mpg.de
Shvedunova, Maria

phone: -707 / -705

shvedunova@ie-freiburg.mpg.de
Turley, Matthew

phone: -694

turley@ie-freiburg.mpg.de
Technicians

Holz, Herbert

phone: -695

holz@ie-freiburg.mpg.de
Stehle, Thomas

phone: -514

stehle@ie-freiburg.mpg.de

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