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...
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
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 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...
-
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...
-
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...
Recent Publications
-
Msl1-Mediated Dimerization of the Dosage Compensation Complex Is Essential for Male X-Chromosome Regulation in Drosophila.
Hallacli, E., Lipp, M., Georgiev, P., Spielman, C., Cusack, S. Akhtar, A., and Kadlec, J. (2012)
Mol.Cell 48, 587-600 -
Drosophila Dosage Compensation Involves Enhanced Pol II Recruitment to Male X-Linked Promoters
Conrad, T., Cavalli F.M., Vaquerizas, J.M., Luscombe, N.M., Akhtar, A. (2012)
Science. 337, 742 - 746 -
The NSL Complex Regulates Housekeeping Genes in Drosophila.
Lam, KC., Mühlpfordt, F., Vaquerizas, J.M., Raja, S.J., Holz, H., Luscombe, N.M., Manke, T., Akhtar, A. (2012)
PLoS Genet. 8(6):e1002736. Epub 2012 Jun 14. -
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 -
The nucleus and gene expression: the center of the cyclone
Akhtar A, Neugebauer K (2012)
Curr Opin Cell Biol. 2012 Jun;24(3):293-5 -
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 -
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 -
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, Asifaphone: -565
-
Administrative Assistant
Schmidl, Lindaphone: -564
-
Postdoctoral Fellows
Aktas Ilik, Tugcephone: -707
-
Chlamydas, Sarantisphone: -707
-
Georgiev, Plamenphone: -705
-
Hallacli, Erincphone: -692
-
Herquel, Benjaminphone: -694 / -707
-
Ilik, Ibrahim Avsarphone: -692
-
Karpiuk, Oleksandraphone: -707
-
Khanam, Tasneemphone: -704
-
Lucci, Jacopophone: -693
-
Toscano, Sarahphone: -691
-
Ph.D. Students
Chatterjee, Aindrilaphone: -694
-
Chelmicki, Tomaszphone: -694
-
Gaub, Alinephone: -582
-
Lam, Kenphone: -514
-
Lingg, Thomasphone: -695
-
Nguyen, Nhuongphone: -582
-
Panhale, Amolphone: -691
-
Semplicio, Giuseppephone: -707
-
Shvedunova, Mariaphone: -707 / -705
-
Turley, Matthewphone: -694
-
Technicians
Holz, Herbertphone: -695
-
Stehle, Thomasphone: -514
