compared with T cells from healthy individuals. In contrast to the effects observed at the IL2 gene locus, CREMα recruits less HDAC1 and DNMT3a to the IL17A promoter, contributing to an overall increase in histone H3 acetylation and reduced histone H3 methylation, as well as CpG hypomethylation of the IL17 locus. Indeed, CREMα overexpression in human T cells increases histone H3 acetylation while it decreases histone H3 methylation and meCpG levels over the entire IL17 gene locus in a yet-to-be determined manner (T. Rauen and C.M. Hedrich, unpublished and [34]). This is in agreement with the finding that in addition to its transcriptional effects, the activating isoform CREMτ mediates increases in histone H3 acetylation in male germ cells [50]. Furthermore, forced CREMα expression in human T lymphocytes results in CpG de-methylation of the IL17A promoter, mimicking the situation in T lymphocytes from SLE patients, which display almost complete de-methylation of the IL17A proximal promoter [44,51]. Thus, CREMα regulates the remodeling of the IL17 gene into an open, accessible state, which allows additional transcription factors to bind. The exact mechanisms by which CREMα mediate histone acetylation in this region while mediating diametric histone modification around the IL2 gene remains to be
