The control of gene expression depends on the access of chromatin gene regulatory areas to the transcriptional machinery. The covalent modifications of histones as acetulaciones and methylation are key factors to regulate that access. Reading the information contained in these posttranslational modifications of histones depends on the function of effector proteins. Therefore, understanding the mechanisms of recognition of these effectors and how histone modification patterns result in complex patterns of expression is key to understanding the transcriptional process.

The trimethylation of histone H3 at residue lysine 4 (H3K4me3) is a crucial signal activation of gene expression. ORC1 protein is the subunit complex recognition of the origins of DNA replication. Besides, in yeast and humans, ORC1 functions as a transcriptional repressor of certain genes such as c-Myc in humans.Work by Maria de la Paz Sanchez and Crisanto Gutierrez of the Center for Molecular Biology ‘Severo Ochoa’, ORC1 has established that also functions as a transcriptional activator of certain genes in the plant Arabidopsis thaliana, a surprising result given the conservation of amino acids and structural domains between yeast, human and plants.

The structural basis of the role of ORC1 is the presence of a PHD domain at the N-terminal is able to interact specifically with residues H3K4me3 promoters of target genes. This binding is associated with increased acetylation of histone H4 and trimethylation of residue K20 of histone H4 (H4K20me3). The paper concludes that, unlike what happens in humans, H4K20me3 is associated with activation and not repression transcipcional. These data provide a molecular basis to explain ORC1 opposing functions in transcriptional regulation. The work also reveals that ORC1 would be a new class of effectors that bind H3K4me3 and activate transcription in all vegetable organisms.