It has become clear that CREMα orchestrates tissue-specific expression of the IL2 and IL17A genes, CREMα contributes to the silencing of IL2 through trans-repression and tissue- and region-specific recruitment of specific DNA and histone methyltransferases or HDACs. Conversely, CREMα trans-activates IL17A and mediates epigenetic remodeling with reduced meCpG and increased histone H3 acetylation in a yet-to-be determined manner [34,42,44]. At present, the molecular mechanisms directing these functional differences remain to be determined. Tissue- and region-specific differences could be mediated by blocking DNA methylation of the daughter-strand during cell division and subsequent translation into the histone code or through the tissue-specific interaction with DNA de-methylases and histone acetyltransferases. Those functional differences could be directed by the proximity to further transcription factors allowing or prohibiting the recruitment of epigenetic activators or repressors.
