Ashlesha previously worked on understanding regulation of the master transcriptional regulator SIN3, which is conserved from yeast to mammals. She found an interesting interplay between the predominant isoforms of SIN3 in Drosophila melanogaster that possibly regulates the overall level of SIN3 in the cell. She also investigated whether the histone modifying complexes associated with SIN3 isoforms establish distinct histone modification patterns at target genes. Her work provides insight into the non-redundant roles of these isoforms, which is critical, since the mammalian SIN3 isoforms are known to play differential roles in cancer progression.
Ashlesha is currently investigating the mechanisms underlying transcriptional regulation of histone mRNA synthesis. In Drosophila, there are approximately 100 copies of the histone gene unit (one copy each of His2A, His2B, His3, His4 and His1) tandemly arrayed at a single locus on chromosome 2. Intriguingly, a single transgene containing just 12 copies of the histone unit in a synthetic gene array is sufficient to compensate for the loss of ~200 histone genes in a diploid fly. She is interested in deciphering this histone gene dosage compensation using a variety of molecular and genetic approaches.