Histone H3 Lysine 4 and 27 Trimethylation Landscape of Human Alzheimer’s Disease
Giuseppe Persico,
Francesca Casciaro,
Stefano Amatori,
Martina Rusin,
Francesco Cantatore,
Amalia Perna,
Lavinia Alberi Auber,
Mirco Fanelli,
Marco Giorgio
Affiliations
Giuseppe Persico
Department of Experimental Oncology, IRCCS—European Institute of Oncology, Via Adamello 16, 20139 Milano, Italy
Francesca Casciaro
Department of Biomedical Sciences, University of Padua, Via Ugo Bassi 58/B, 35131 Padova, Italy
Stefano Amatori
Molecular Pathology Laboratory “PaoLa”, Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Arco d’Augusto 2, 61032 Fano (PU), Italy
Martina Rusin
Department of Experimental Oncology, IRCCS—European Institute of Oncology, Via Adamello 16, 20139 Milano, Italy
Francesco Cantatore
Molecular Pathology Laboratory “PaoLa”, Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Arco d’Augusto 2, 61032 Fano (PU), Italy
Amalia Perna
Department of Pathology, School of Medicine, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA
Lavinia Alberi Auber
Swiss Integrative Center of Human Health, Pass. du Cardinal 13, 1700 Fribourg, Switzerland
Mirco Fanelli
Molecular Pathology Laboratory “PaoLa”, Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Arco d’Augusto 2, 61032 Fano (PU), Italy
Marco Giorgio
Department of Experimental Oncology, IRCCS—European Institute of Oncology, Via Adamello 16, 20139 Milano, Italy
Background: Epigenetic remodeling is emerging as a critical process for both the onset and progression of Alzheimer’s disease (AD), the most common form of neurodegenerative dementia. However, it is not clear to what extent the distribution of histone modifications is involved in AD. Methods: To investigate histone H3 modifications in AD, we compared the genome-wide distributions of H3K4me3 and H3K27me3 in entorhinal cortices from severe sporadic AD patients and from age-matched healthy individuals of both sexes. Results: AD samples were characterized by typical average levels and distributions of the H3K4me3 and H3K27me3 signals. However, AD patients showed a lower H3K4me3 and higher H3K27me3 signal, particularly in males. Interestingly, the genomic sites found differentially trimethylated at the H3K4 between healthy and AD samples involve promoter regions of genes belonging to AD-related pathways such as glutamate receptor signaling. Conclusions: The signatures of H3K4me3 and H3K27me3 identified in AD patients validate the role of epigenetic chromatin remodeling in neurodegenerative disease and shed light on the genomic adaptive mechanisms involved in AD.
