Evidence for an intronic cis-regulatory element within CD69 gene.

CD69 is one of the earliest proteins expressed after leukocyte activation and its engagement is essential in the control of innate and adaptive immune responses. Inducible CD69 expression is strongly controlled at the transcriptional level. The molecular basis for developmental- and stage-specific regulation in T cells is beginning to be elucidated while it remains largely unknown in the rest of immune cells. DNase I hypersensitivity experiments in lymphocytes identified a novel hypersensitive region within mouse and human intron I, which was inducible upon stimulation. In silico analysis of CD69 gene revealed that this open chromatin region was present in different cell types and was associated with positioned nucleosomes. Analysis of histone post-translational modifications of intron I indicated that acetylation and lysine 4 dimethylation of histone H3 were dynamically regulated during thymocyte development and were constitutively high in resting and stimulated mature T lymphocytes. Thus, we provide evidence for the existence of a cis-acting element in intron I that is more accessible to DNase I digestion and that it is developmentally regulated at the chromatin level.