The role of Toll-like receptors in chronic B cell malignancies

Toll-like receptors (TLR) are key players in host defence from infection. They recognize a specific set of molecular patterns of microbial origin, immediately trigger an innate immune response, and bridge innate and adaptive immunity. TLR have also been shown to play a role in tumor development. In this context, chronic B-cell malignancies are an interesting example as clonal B lymphocytes remain responsive to and dependent on stimuli originating from the microenvironment which then become crucial for maintaining and propagating the disease. Emerging evidences suggest that, among other microenvironmental elements, TLR ligands may play a role in the pathogenesis of chronic B-cell lymphoid malignancies. Conceivably, their manipulation may find a place in specific settings of treatment of these tumors

H3K4me3 demethylation by the histone demethylase KDM5C/JARID1C promotes DNA replication origin firing

International audienceDNA replication is a tightly regulated process that initiates from multiple replication origins and leads to the faithful transmission of the genetic material. For proper DNA replication, the chromatin surrounding origins needs to be remodeled. However, remarkably little is known on which epigenetic changes are required to allow the firing of replication origins. Here, we show that the histone demethylase KDM5C/JARID1C is required for proper DNA replication at early origins. JARID1C dictates the assembly of the pre-initiation complex, driving the binding to chromatin of the pre-initiation proteins CDC45 and PCNA, through the demethylation of the histone mark H3K4me3. Fork activation and histone H4 acetylation, additional early events involved in DNA replication, are not affected by JARID1C downregulation. All together, these data point to a prominent role for JARID1C in a specific phase of DNA replication in mammalian cells, through its demethylase activity on H3K4me3