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 plays an essential role in the regulation of gene expression. Structural changes in chromatin 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.
One of our major goals 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 at a single cell resolution all the way to chromosomal and organismal level.