The Enigma of Silencing and Turning on Genes
Dr. Jawad Akhtar's PhD in the LUMS Epigenetics Lab
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The process of human development is a very fascinating phenomenon which has also intrigued philosophers and scientists to think and discover the underlying intricacies. In other words, an average human body, that arises from a single fertilized egg, contains roughly 30 trillion cells which undergo about 10 quadrillion rounds of division throughout our lifetimes. To add to this intricacy, our body is not made up of identical cells but contain more than two hundred different highly specialized cell types that are responsible for the development of complex organs like heart, kidney, liver, eyes and brain.
Although each cell type contains the same basic genetic information (DNA) they inherit from the fertilized egg, their identities and functions
are drastically different from one another. Despite sharing the same set of genetic code, all the different cell types in a human body arise due to differences in their gene expression (decoding of gene) state. Such specific decoding of information gives each cell its identity which is maintained by two groups of highly specialized proteins, namely trithorax group (trxG) and Polycomb group (PcG).
The PcG proteins are known to maintain genes in an OF state whereas trxG are known to antagonize PcG and maintain genes in an ON state, thus helping cells remember their fates. The maintenance of gene activation (ON state) by trxG is known as a constant struggle by proteins in the trxG against a default state of gene silencing maintained by the PcG.
During his PhD under Dr. Muhammad Tariq’s supervision, Jawad Akhtar worked on PcG/trxG paradigm using fruit flies. He specifically worked on a gene named Enok in flies which is known to modify fundamental building blocks of chromosomes and facilitate gene activation. Jawad’s work has discovered a complex interplay between Enok and PcG factors which results in suppression of gene silencing by PcG and contributes to the anti-silencing act of the trxG. Using a functional genomics approach and employing molecular and biochemical tools, Jawad discovered that Enok physically associates with genes which are normally bound by trxG factors. However, his work categorically established that while associating with chromatin, Enok actually inhibits the repressive effect of specific factors in PcG and consequently helps trxG. Jawad’s work has certainly discovered a hitherto unknown role for Enok in maintenance of gene activation linked to the maintenance of cell fates and cellular memory. It also highlights a fact that dynamic and regulated cross-talk between PcG and trxG is quite complex and it will take time before we fully understand molecular
mechanism of gene activation maintained by the trxG.
A recently published article in Epigenetics and Chromatin Journal https://link.springer.com/article/10.1186/s13072-019-0301-x describes details of Jawad’s work which was performed under supervision of Dr. Muhammad Tariq in Epigenetics lab. This work in Tariq lab was funded by grants from the Higher Education Commission and LUMS.
