Genetic and Molecular Analysis uncovers a novel role for Drosophila Enok in Maintenance of Epigenetic Cell Memory
Genetic analysis described here reveals that mutants of both enok and Br140 strongly suppressed extra sex comb phenotype of Pc mutants and enhanced homeotic transformations associated with trx mutations. This trxG like behavior of Enok was further substantiated by the fact that depletion of either enok or Br140 with concomitant loss of H3K23ac resulted in reduced expression of trxG target genes. This downregulation of trxG targets was accompanied by an increased enrichment of PC and mono-ubiquitination of histone H2A at lysine 118 which is a known hallmark of PcG. Moreover, depletion of Enok also resulted in an increased stalling of RNA Pol-II in the promoter region of trxG target genes. Although Enok was found to colocalize with both TRX and PC at the chromatin, it was discovered that Enok specifically counteracts PRC1 mediated repression. Together, genetic and molecular analysis described in this dissertation demonstrates that Enok complex specifically contributes to the maintenance of gene activation by counteracting PcG. Further, molecular and biochemical characterization of H3K23ac by Enok and its cross-talk with covalent modifications of histones catalyzed by trxG and PcG will help understand how it is required for maintenance of gene activation by trxG.
Umer, Z*., Akhtar, J*., Khan, MHF*., Shaheen, N., Haseeb, MA., Mazhar, K., Mithani, A., Anwar, S and Tariq, M. (2019). Genome-wide RNAi screen in Drosophila reveals Enok as a novel Trithorax group regulator. Epigenetics and Chromatin 12, 55 (2019) doi:10.1186/s13072-019-0301-x
*: Equal authors