Post-translational modifications (PTMs) of the histone H3 tail in response to stress represent highly conserved epigenetic processes. However, the regulatory function of histone phosphorylation was hardly studied in post-mitotic cardiomyocytes. By a series of in vitro and in vivo experiments, we identified CaMKII as a catecholamine-sensitive kinase that phosphorylates H3S28. Whereas in CaMKII-deficient myocytes acute catecholaminergic stimulation resulted in some degree of H3S28p, sustained catecholaminergic stimulation almost entirely failed to induce H3S28p. Genome-wide analysis of CaMKII-mediated H3S28p in response to chronic β-AR stress by chromatin-immunoprecipitation followed by massive genomic sequencing led to the identification of CaMKII-dependent H3S28p target genes. 40% of differentially H3S28p-enriched genomic regions were associated with differential, mostly increased expression of the nearest genes, pointing to CaMKII-dependent H3S28p as an activating histone mark. Surprisingly, among the CaMKII-dependent H3S28p-regulated genes we  found alpha- and beta-globins. Expression analyses confirmed that hemoglobin is expressed in cardiomyocytes in a CaMKII-dependent manner. This study raises important questions about the functional role of hemoglobin in non-hematopoietic cells such as cardiomyocytes but also about the general role of CaMKII for hematopoesis.