Oxygen depleted tissues can be found in flooded plants, but are also common in metabolically active regions embedded in the plant body. Oxygen sensing occurs through an oxygen-dependent modification of cysteine placed in second position of ERF-VII transcription factors, which sends these proteins to proteasomal degradation. In animals hypoxia has been correlated to the maintenance of an undifferentiated state in stem cells. To investigate potential oxygen-dependent regulations of stem cells in plants, we studied the structure and expression of two little zipper proteins (ZPR1/2), which are characterized by a conserved N-terminal cysteine residue. We especially focused on their role in the regulation of HD-ZIP III, a family of transcription factors involved in shoot apical meristem development. We found that ZPR1/2 are expressed in the meristem and are able to regulate transcriptional activity of three out of five HD-ZIP III on selected targets. We propose that ZPR1/2 are stabilized in an hypoxic niche inside the meristem, where they downregulate HD-ZIP III activity and therefore confine it to the external layers. Further roles in other contexts are also proposed