Histone H1 protects telomeric repeats from H3K27me3 invasion in Arabidopsis.

While the pivotal role of linker histone H1 in shaping nucleosome organization is well established, its functional interplays with chromatin factors along the epigenome are just starting to emerge. Here we show that, in Arabidopsis, as in mammals, H1 occupies Polycomb Repressive Complex 2 (PRC2) target genes where it favors chromatin condensation and H3K27me3 deposition. We further show that, contrasting with its conserved function in PRC2 activation at genes, H1 selectively prevents H3K27me3 accumulation at telomeres and large pericentromeric interstitial telomeric repeat (ITR) domains by restricting DNA accessibility to Telomere Repeat Binding (TRB) proteins, a group of H1-related Myb factors mediating PRC2 cis recruitment. This study provides a mechanistic framework by which H1 avoids the formation of gigantic H3K27me3-rich domains at telomeric sequences and contributes to safeguard nucleus architecture.

Contribution of 3D genome topological domains to genetic risk of cancers: a genome-wide computational study.

BACKGROUND: Genome-wide association studies have identified statistical associations between various diseases, including cancers, and a large number of single-nucleotide polymorphisms (SNPs). However, they provide no direct explanation of the mechanisms underlying the association. Based on the recent discovery that changes in three-dimensional genome organization may have functional consequences on gene regulation favoring diseases, we investigated systematically the genome-wide distribution of disease-associated SNPs with respect to a specific feature of 3D genome organization: topologically associating domains (TADs) and their borders. RESULTS: For each of 449 diseases, we tested whether the associated SNPs are present in TAD borders more often than observed by chance, where chance (i.e., the null model in statistical terms) corresponds to the same number of pointwise loci drawn at random either in the entire genome, or in the entire set of disease-associated SNPs listed in the GWAS catalog. Our analysis shows that a fraction of diseases displays such a preferential localization of their risk loci. Moreover, cancers are relatively more frequent among these diseases, and this predominance is generally enhanced when considering only intergenic SNPs. The structure of SNP-based diseasome networks confirms that localization of risk loci in TAD borders differs between cancers and non-cancer diseases. Furthermore, different TAD border enrichments are observed in embryonic stem cells and differentiated cells, consistent with changes in topological domains along embryogenesis and delineating their contribution to disease risk. CONCLUSIONS: Our results suggest that, for certain diseases, part of the genetic risk lies in a local genetic variation affecting the genome partitioning in topologically insulated domains. Investigating this possible contribution to genetic risk is particularly relevant in cancers. This study thus opens a way of interpreting genome-wide association studies, by distinguishing two types of disease-associated SNPs: one with an effect on an individual gene, the other acting in interplay with 3D genome organization.

The 3D Organization of Chromatin Colors in Mammalian Nuclei.

While many computational methods have been proposed for 3D chromosome reconstruction from chromosomal contact maps, these methods are rarely used for the interpretation of such experimental data, in particular Hi-C data. We posit that this is due to the lack of an easy-to-use implementation of the proposed algorithms, as well as to the important computational cost of most methods. We here give a detailed implementation of the fast ShRec3D algorithm. We provide a tutorial that will enable the reader to reconstruct 3D consensus structures for human chromosomes and to decorate these structures with chromatin epigenetic states. We use this methodology to show that the bivalent chromatin, including Polycomb-rich domains, is spatially segregated and located in between the active and the quiescent chromatin compartments.

Improving distance measures between genomic tracks with mutual proximity.

An increasing number of genomic tracks such as DNA methylation, histone modifications or transcriptomes are being produced to annotate genomes with functional states. The comparison of such high dimensional vectors obtained under various experimental conditions requires the use of a distance or dissimilarity measure. Pearson, Cosine and $L_{p}$-norm distances are commonly used for both count and binary vectors. In this article, we highlight how enhancement methods such as the contrast increasing mutual proximity' (MP) or local scaling' improve common distance measures. We present a systematic approach to evaluate the performance of such enhanced distance measures in terms of separability of groups of experimental replicates to outline their effect. We show that the MP' applied on the various distance measures drastically increases performance. Depending on the type of epigenetic experiment, MP' coupled together with Pearson, Cosine, $L_1$, Yule or Jaccard distances proves to be highly efficient in discriminating epigenomic profiles.