Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters.

Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation.

Interferon-beta administration confers a beneficial outcome in a rabbit model of thromboembolic cerebral ischemia.

We demonstrate that treatment with the cytokine human interferon-beta (IFN-beta) resulted in a beneficial outcome in a rabbit model of thromboembolic cerebral ischemia. Rabbits administered subcutaneously with IFN-beta prior to (pre-treatment) or after (post-treatment) the introduction of an autologous blood clot into the middle cerebral artery have consistently smaller subcortical infarct volumes compared to control (untreated) counterparts. The average subcortical infarct volume of pre-treatment rabbits is 46.3+/-9.3 mm(3) (n=4), and that of post-treatment rabbit is 40.0+/-23.1 mm(3) (n=4). Both are significantly lower (P=0.003 and P=0.004, respectively) than the average subcortical infarct volume of control rabbits (121.6+/-32.9 mm(3), n=5). Although the precise mechanism responsible for the beneficial effect of IFN-beta on stroke is not yet clear, our results are in line with the known anti-inflammatory potential and anti-apoptotic function of IFN-beta.