QRICH1 Dictates the Outcome of ER Stress through Transcriptional Control of Proteostasis [ChIP-seq]

Perturbation of tissue homeostasis accompanies a diversity of inflammatory pathologies and imposes metabolic constraints at the cellular level that elicit ER stress, protein misfolding, and cell death. In response to ER stress, cells initiate the unfolded protein response (UPR), which determines divergent cell fate decisions, either promoting recovery of ER proteostasis and cell survival or triggering programmed cell death. However, the mechanisms by which the UPR transitions from the adaptive to terminal state are not fully understood. Here, we identify QRICH1 as a previously uncharacterized transcriptional regulator of a gene modulethat differentially engages the terminal versus adaptive UPR. To prepare the ER-stressed conditions, we treated HT29 wild type or QRICH1 knockout cells with 0.3 ug/ml of Tm for 14 hrs and performed the chromatin immunoprecipitation. Briefly, we fixed the cells with 1% formaldehyde and quenched with glycine. We prepared the cell lysate and sonicated the lysates using sonifier. We incubated the lysate with anti-QRICH1 antibody, anti-ATF4 antibody, or anti-normal rabbit IgG overnight in the cold room. We generated library with three biological replicates.