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Chlamydomonas reinhardtii is a unicellular green alga that can survive at a wide range of inorganic carbon (Ci) concentrations by regulating the activity of a CO₂-concentrating mechanism (CCM) as well as other cellular functions. Under CO₂ limited conditions, C. reinhardtii cells display a wide range of adaptive responses including changes in photosynthetic electron transport, mitochondria localization in the cells, the structure of the pyrenoid starch sheath, and primary metabolism. In addition to these functional and structural changes, gene and protein expression are also affected. Several physiological aspects of the CO₂ response mechanism have been studied in detail. However, the regulatory components (transcription factors and transcriptional regulators) involved in this process are not fully characterized. Here we report a comprehensive analysis of the C. reinhardtii nuclear proteome using liquid chromatography electrospray ionization spectrometry (LC-ESI-MS). The study aims to identify the proteins that govern adaptation to varying CO₂ concentrations in Chlamydomonas. The nuclear proteome of C. reinhardtii cells grown in the air at high (5%) and low (0.04%) CO₂ concentrations were analyzed. Using this approach, we identified 1378 proteins in total, including 90 putative transcription factors and 27 transcriptional regulators. Characterization of these new regulatory components could shed light on the molecular mechanisms underlying acclimation to CO₂ stress.