THE TRANSCRIPTIONAL PROGRAM OF GOLGI BIOGENESIS

The Golgi apparatus is considered a fundamental organelle that regulates various physiological processes. Due to its plasticity, it can expand during differentiation and in response to high secretory demand. However, transcriptional contribution to Golgi biogenesis remains poorly understood because of the lack of a robust method to induce large-scale production of new Golgi units. In this study, we developed an enzyme-based approach to eliminate the Golgi apparatus, triggering the de novo formation of fully functional stacks in a substantial cohort of cells within 10-18 hours. The structural and functional recovery of the Golgi allowed us to study transcriptomic changes associated with Golgi regeneration. Indeed, Single-cell RNA-seq of cells rebuilding the Golgi revealed coordinated induction of a broad Golgi gene network, coinciding with structural and functional organelle maturation. The upregulated Golgi genes encode proteins belonging to different compartments (cis-, medial-, and trans-Golgi), which are involved in diverse functions such as glycosylation, membrane tethering, and ion/sugar transport. These findings suggest the existence of a master regulator that orchestrates the simultaneous expression of components required for the structural and functional integrity of the organelle. Through bioinformatic and in vitro analysis, we identified CREB3L1 as a key transcriptional regulator that activates a Golgi gene network and drives organelle rebuilding. Our findings demonstrate that CREB3L1 activation initiates a transcriptional program essential for complete Golgi biogenesis program, which may be critical for organelle regeneration and remodulation.