Biology subjects

Li Wang, X.

Publications and source records attributed to Li Wang, X..

3 recordsLinked to original sources

bioRxiv2026

The human RNA-DNA interactome is cell type-specific and dynamic

More than twenty years ago, the FANTOM consortium uncovered that mammalian genomes are pervasively transcribed, revealing multitudes of RNAs with unknown functions. A subset of these transcripts has since then been linked to transcriptional control and to chromatin organization via their ability to interact with DNA, suggesting that chromatin-associated RNAs could be key players in genome regulation. Although recent technological advances now enable the mapping of genome-wide RNA-DNA contacts, a lack of analyses integrating these methods with other genomic features and across multiple cellular contexts hinders our comprehensive understanding of the principles underlying RNA-DNA interactions and of their biological importance. As part of the FANTOM6 project, we thus generated RNA-DNA interaction maps in 16 different human cell types, then combined these contacts with multiple layers of other genomic data to investigate how patterns of interaction between RNA and DNA relate to chromatin organization and function. We show that the RNA-DNA interactome is highly dynamic yet reproducibly organized in cell-type specific networks, constituted of a great diversity of interactions that vary in function of their distance, the nature of their sources and the chromatin state of their targets. In particular, we detected numerous regulatory elements that exhibit marked changes in activity when differentially bound by transcripts, implying that thousands of RNA-DNA interactions can play a mechanistic role in gene expression. This regulatory function correlates with RNA-protein interactions and significantly associates with cell type-relevant and disorder-related traits. In addition to providing essential resources for future research in RNA-mediated chromatin regulation, cellular biology and human diseases, our study thus establishes the RNA-DNA interactome as a new genome regulatory layer that defines and maintains cellular identity and behavior.

genomics↗

bioRxiv2022

FOXO dictates initiation of B cell development and myeloid restriction in common lymphoid progenitors

The development of B cells relies on an intricate network of transcription factors critical for developmental progression and lineage commitment. In the B cell developmental trajectory, a temporal switch from predominant Foxo3 to Foxo1 expression occurs at the CLP stage. Utilizing VAV-iCre mediated conditional deletion, we found that the loss of FOXO3 impaired B cell development from LMPP down to B cell precursors, while the loss of FOXO1 impaired B cell commitment and resulted in a complete developmental block at the CD25 negative proB cell stage. Strikingly, the combined loss of FOXO1 and FOXO3 resulted in the failure to restrict the myeloid potential of CLPs and the complete loss of the B cell lineage. This is underpinned by the failure to enforce the early B-lineage gene regulatory circuitry upon a predominantly pre-established open chromatin landscape. Altogether, this demonstrates that FOXO3 and FOXO1 cooperatively govern early lineage restriction and initiation of B-lineage commitment in CLPs. SUMMARYCommon lymphoid progenitors co-express the transcription factors FOXO1 and FOXO3. Removing FOXO1 and FOXO3 at this developmental stage results in regained myeloid potential, failed establishment of the early B cell gene regulatory program, and the complete loss of the B cell lineage.

immunology↗

bioRxiv2020

Convergent Met and voltage-gated Ca2+ channel signaling on Ras-Erk MAPK drives migratory activation of dendritic cells parasitized by Toxoplasma gondii

Ras-Erk MAPK signaling controls many of the principal pathways involved in metazoan cell motility, drives metastasis of multiple cancer types and is targeted in chemotherapy. Yet, its putative roles in immune cell functions or in infections have remained elusive. Here, using primary dendritic cells (DCs) in an infection model with the protozoan Toxoplasma gondii, we show that two pathways activated by infection converge on Ras-Erk MAPK signaling to promote migration of parasitized DCs. We identify signaling through the receptor tyrosine kinase Met (also known as HGFR) as a driver of T. gondii-induced DC hypermotility. Further, we show that voltage-gated Ca2+channel (VGCC, subtype CaV1.3) signaling impacts the migratory activation of DCs via calmodulin-calmodulin kinase II. We report that VGCC and Met signaling converge on Ras GTPase to drive Erk1/2 phosphorylation and migratory activation of T. gondii-infected DCs. The data provide a molecular basis for the hypermigratory mesenchymal-to-amoeboid transition (MAT) of parasitized DCs. The emerging concept suggests that parasitized DCs acquire metastasis-like migratory properties to promote infection-related dissemination.

cell biology↗