WOJCIECH SIWEK

Proper regulation of gene expression is fundamental for multicellular life. In my research, I am interested in how cells maintain active gene expression states. Preservation of gene expression can be regulated in cis, by non-diffusible stretches of DNA; or in trans by diffusible proteins capable of DNA binding. Chromatin is at the center of cis-acting feedback loops that control maintenance of silencing. Dedicated cellular machinery is employed to read and copy chromatin marks to maintain the silent state during replication and mitosis. On the other hand, mechanisms controlling maintenance of active transcription often rely on feedback loops involving trans-acting transcription factors. In these loops, induced transcription factors activate their own expression indefinitely. Trans-acting transcription factor feedback loops can maintain active states, but are not always required. This suggests that other, possibly cis-acting, processes (similar to those in silencing) are involved in preserving active transcriptional states. Strikingly, such mechanisms are poorly understood. This knowledge gap comes from the fact that uncoupling transcription factor driven expression from maintenance of expression states is difficult to achieve experimentally. I am exploring a phenomenon present in the innate immune system – transcriptional memory to accomplish such uncoupling and gain access to new cis-acting mechanisms regulating maintenance of active gene expression states. Transcriptional memory is a process during which cells exposed to a certain cue (induction) will remember the experience and respond to the second stimulation with the same signal (reinduction) more strongly. I am studying how this process is established and maintained in human cells.