RESUMEN
DNA and histone modifications combine into characteristic patterns that demarcate functional regions of the genome1,2. While many 'readers' of individual modifications have been described3-5, how chromatin states comprising composite modification signatures, histone variants and internucleosomal linker DNA are interpreted is a major open question. Here we use a multidimensional proteomics strategy to systematically examine the interaction of around 2,000 nuclear proteins with over 80 modified dinucleosomes representing promoter, enhancer and heterochromatin states. By deconvoluting complex nucleosome-binding profiles into networks of co-regulated proteins and distinct nucleosomal features driving protein recruitment or exclusion, we show comprehensively how chromatin states are decoded by chromatin readers. We find highly distinctive binding responses to different features, many factors that recognize multiple features, and that nucleosomal modifications and linker DNA operate largely independently in regulating protein binding to chromatin. Our online resource, the Modification Atlas of Regulation by Chromatin States (MARCS), provides in-depth analysis tools to engage with our results and advance the discovery of fundamental principles of genome regulation by chromatin states.
Asunto(s)
Ensamble y Desensamble de Cromatina , Cromatina , Proteínas Nucleares , Nucleosomas , Proteómica , Humanos , Sitios de Unión , Cromatina/química , Cromatina/genética , Cromatina/metabolismo , ADN/genética , ADN/metabolismo , Elementos de Facilitación Genéticos , Heterocromatina/genética , Heterocromatina/metabolismo , Histonas/metabolismo , Proteínas Nucleares/análisis , Proteínas Nucleares/metabolismo , Nucleosomas/química , Nucleosomas/genética , Nucleosomas/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , Proteómica/métodosRESUMEN
This paper presents a model that allows group comparisons of gaze behavior while watching dynamic video stimuli. The model is based on the approach of Coutrot and Guyader (2017) and allows linear combinations of feature maps to form a master saliency map. The feature maps in the model are, for example, the dynamically salient contents of a video stimulus or predetermined areas of interest. The model takes into account temporal aspects of the stimuli, which is a crucial difference to other common models. The multi-group extension of the model introduced here allows to obtain relative importance plots, which visualize the effect of a specific feature of a stimulus on the attention and visual behavior for two or more experimental groups. These plots are interpretable summaries of data with high spatial and temporal resolution. This approach differs from many common methods for comparing gaze behavior between natural groups, which usually only include single-dimensional features such as the duration of fixation on a particular part of the stimulus. The method is illustrated by contrasting a sample of a group of persons with particularly high cognitive abilities (high achievement on IQ tests) with a control group on a psycholinguistic task on the conceptualization of motion events. In the example, we find no substantive differences in relative importance, but more exploratory gaze behavior in the highly gifted group. The code, videos, and eye-tracking data we used for this study are available online.
