Mukulika Ray, Postdoctoral Researcher
Temperature is one important abiotic regulator of gene expression that substantially affects biological functions. How increasing temperature affects gene transcription has not only helped us understand the process of transcription per se but is vital for managing the effects of global changes in temperature on living organisms, including humans, plants, and animals, for economic purposes.
Heat stress (HS), caused by increasing temperature beyond physiological limits, leads to activation of stress response genes and repression of constitutive gene expression, both essential for cell survival. Heat shock is an excellent model for understanding the mechanisms of transcription. A key question is: How are genes specifically targeted for activation or repression upon heat stress? Although extensive studies have elucidated the mechanisms that drive HS-induced activation of stress response genes, little is known about the mechanisms that repress thousands of constitutive genes. The mechanisms of heat shock-regulated transcription have been first and most thoroughly studied in Drosophila which we used as our model system where the GA-binding TF GAF was shown to be essential for activation of genes upon heat stress. Here, we show that another GA-binding transcription factor (TF) protein CLAMP (Chromatin-linked adaptor for MSL complex proteins) that can compete with GAF for its binding sites is essential for repression of constitutive genes upon heat stress. We also identified CLAMP-associated 3D loop anchors using Hi-ChIP both before and after heat shock. Furthermore, CLAMP-bound loop anchors that overlap with genes that are normally actively transcribed and and then become repressed after heat shock are characterized by a different set of chromatin marks and interacting TFs than, those which are normally paused and become activated after HS. Overall, we propose that the function of different GA-binding TFs in mediating 3D interactions distinguish genes that are activated from those that are repressed upon heat stress.