Spatial and Temporal Expression of High Mobility Group Nucleosome‐Binding (HMGN) Genes in Brain Areas Associated with Cognition in Individuals with Down Syndrome

Background DNA methylation and histone posttranslational modifications are epigenetics processes that contribute to Down Syndrome (DS) neurophenotype. Previous reports present strong evidence that High Mobility Group Nucleosome‐binding (HMGN), which is a group of nonhistone proteins, are epigenetic regulators. HMGNs play important functions in several processes to maintain brain homeostasis. We aimed to analyze the differential expression of five human HMGN genes along some brain structures and age ranks from DS postmortem brain samples. Methodology We performed a computational analysis of five human HMGN expression from a DNA microarray experiment data (GEO database ID GSE59630). Using the transformed log2 data, we analyzed the differential expression for HMGN human genes along several brain areas which are associated with cognition processes in individuals with DS. Moreover, using information from several genome databases, we explore their coexpression and protein interaction with the histones of the nucleosome core particle and linker H1 histone. Results We registered that HMGN1 and HMGN5 were significantly overexpressed in the hippocampus and some structures of the prefrontal cortex in DS individuals. Age ranks comparisons between euploid control and trisomic individuals showed that HMGN2 and HMGN4 were overexpressed in the DS brain of 16 to 22 weeks of gestation. From the BioGRID database, we registered high interaction scores of HMGN2 and HMGN4 with Hist1H1A and Hist1H2BA, Hist2AG and Hist1H3A, respectively. Conclusions Overall our results give strong evidence to propose that DS would be an epigenetics‐based aneuploidy in which the remodeling the brain chromatin by HMGN1 and HMGN5, would essential pathways in the alteration of brain homeostasis in DS.