Highlights d A database combining genomic information and chromatin profiles for Marchantia d Correlations between chromatin marks and transcription are conserved in land plants d A significant portion of constitutive heterochromatin is marked by H3K27me3 d Insights into the evolution of TAD organization in plants

A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.

Ctf4 is a protein conserved in eukaryotes and a constituent of the replisome progression complex. It also plays a role in the establishment of sister chromatid cohesion. In our current study, we demonstrate that the replication checkpoint is activated in the absence of Ctf4, and that the interaction between the MCM helicase-go ichi ni san (GINS) complex and DNA polymerase alpha (Pol alpha)-primase is destabilized specifically in a ctf4Delta mutant. An in vitro interaction between GINS and DNA Pol alpha was also found to be mediated by Ctf4. The same interaction was not affected in the absence of the replication checkpoint mediators Tof1 or Mrc1. In ctf4Delta cells, DNA pol alpha became significantly unstable and was barely detectable at the replication forks in HU. In contrast, the quantities of helicase and DNA pol epsilon bound to replication forks were almost unchanged but their localizations were widely and abnormally dispersed in the mutant cells compared with wild type. These results lead us to propose that Ctf4 is a key connector between DNA helicase and Pol alpha and is required for the coordinated progression of the replisome.

Genome packaging by nucleosomes is a hallmark of eukaryotes. Histones and the pathways that deposit, remove, and read histone modifications are deeply conserved. Yet, we lack information regarding chromatin landscapes in extant representatives of ancestors of the main groups of eukaryotes and our knowledge of the evolution of chromatin related processes is limited. We used the bryophyte Marchantia polymorpha, which diverged from 3 vascular plants 400 Mya, to obtain a whole chromosome genome assembly and explore the chromatin landscape and three-dimensional organization of the genome of early land plants.Based on genomic profiles of ten chromatin marks, we conclude that the relationship between active marks and gene expression is conserved across land plants. In contrast, we observed distinctive features of transposons and repeats in Marchantia compared with flowering plants. Silenced transposons and repeats did not accumulate around centromeres, and a significant proportion of transposons were marked by H3K27me3, which is otherwise dedicated to the transcriptional repression of protein coding genes in flowering plants. Chromatin compartmentalization analyses of Hi-C data revealed that chromatin regions belonging to repressed heterochromatin were densely decorated with H3K27me3 but not H3K9 or DNA methylation as reported in flowering plants. We conclude that in early plants, H3K27me3 played an essential role in heterochromatin function, suggesting an ancestral role of this mark in transposon silencing. C C A A CG A G Centromeric repeat Centromeric repeat Centromeric repeat CENP-B box (RC) CENP-B box (RC) CENP-B box (RC) 54 0 17 17 109 162 T