Changed Histone Acetylation Patterns in Normal-Appearing White Matter and Early Multiple Sclerosis Lesions

• DOI: 10.1523/jneurosci.4507-10.2011
• Publication Date: 2011-03-03T20:27:37Z
• Authors: Xiomara Pedre; Fabrizio Mastronardi; Wolfgang Bruck; Gerardo López-Rodas; Tanja Kuhlmann; Patrizia Casaccia
• Keywords: Adult; Aged, 80 and over; Male; Multiple Sclerosis; Acetylation; Middle Aged; Nerve Fibers, Myelinated; Histones; Young Adult; Early Diagnosis; Humans; Female; Aged; Histone Acetyltransferases

The epigenetic identity of oligodendrocytes is modulated by posttranslational modifications histones. Acetylation histone H3 results from the balance between activity acetyltransferases (HATs) and deacetylases modulates transcriptional activation. We have previously shown that, in rodents, deacetylation favors oligodendrocyte differentiation, whereas acetylation associated with increased levels inhibitors differentiation. Here, we report, humans brains, a shift toward white matter frontal lobes aged subjects patients chronic multiple sclerosis (MS). Increased immunoreactivity for acetylated was observed nuclei NogoA+ subset MS samples. These changes were high differentiation (i.e., TCF7L2 , ID2 SOX2 ) higher HAT transcript CBP P300 female compared non-neurological controls correlated disease duration. Chromatin immunoprecipitation samples revealed enrichment acetyl-histone at promoter target genes ). data lesions contrasted findings early lesions, where marked oligodendroglial observed. Together, these suggest that process occurs stages whose efficiency decreases