This review aims to explain why H1 histone can be considered as a protein involved in protecting genomic DNA from full methylation. Some of our results indicated that, to explain the multiple roles in which H1 histone seems to be involved, it is important to consider that it is not a unique protein but a family of genetic somatic variants and that every one of them can be dynamically modified by different post-synthetic enzymatic modifications. Our data show that H1 histone plays an inhibitory effect on DNA methylation through its H1e variant and that poly(ADP-ribosyl)ation is a post-synthetic modification involved in this regulatory role. The idea that the poly(ADP-ribosyl)ated isoform of H1e could be present in decondensed chromatin structure, where the housekeeping genes are located, will be discussed.