Histone H1 or linker histone is involved in the regulation of chromatin structure (4). Histone H1 is part of a multigene family encoding eleven subtypes, seven somatic subtypes, and four germ-line specific subtypes (1). The complement of histone H1 is defined as the subtype composition and their proportions in a cell on a given condition. H1 complement is variable and several studies have reported that is altered in disease, in particular in cancer (2). Therefore, more studies must be performed in order to understand its functions in diseases. In this study the global aim is to understand regulation of the expression of somatic subtypes in human cell lines. Our first objective was to study the role of m6A in the regulation of the mRNA and protein levels of histone H1 subtypes. We used cycloleucine to inhibit METTL3, m6A methyltransferase. We tested several doses finding that in high doses of inhibitor prevent the ability of cells to replicate in the same hour period as untreated cells and effect of cycloleucine is dosedependent in both cell lines. In HEK293T cycloleucine had shown different effects on the cell cycle depending on the dose and the time of treatment. In contrast, in HeLa the distribution of the cell cycle phases was not affected at 24h in any dose. H1 subtypes were differentially affected. At the mRNA level, HeLa cell line showed alteration of mRNA levels that occur in most of the H1 genes and controls at all doses tested, including the lowest dose. At the protein level, changes observed (increase or decrease) are in agreement with changes observed in the mRNA, except for H1.4. Considering the magnitude of the change, there is no correspondence between mRNA and protein levels. In general, the effects are different among subtypes supporting the idea that m6A plays a subtype specific role in H1 regulation. Our second objective was to study the regulation of H1 protein levels by the proteasome in HeLa and HEK293T. We used to inhibitors MG132 and bortezomib. We confirmed that the proteasome is involved in the degradation of H1 subtypes in a subtype- and cell-type specific manner.