Biology subjects

Lopez-Rubio, A. V.

Publications and source records attributed to Lopez-Rubio, A. V..

3 recordsLinked to original sources

bioRxiv2026

TET2-driven activation of AGO2 links epigenetic remodeling to myeloid commitment and leukemia

DNA methylation dynamics shape hematopoietic differentiation and leukemogenesis; yet how the dioxygenase TET2--frequently mutated in myeloid malignancies--directs lineage-specific regulatory programs remains unclear. Here, we integrated DNA methylation, chromatin accessibility, 3D genome architecture, transcriptional profiling, and TET2 chromatin occupancy to define TET2-dependent control of human myeloid commitment. We found that TET2-bound regulatory regions gain short- and long-range chromatin interactions and that a distinct subset of distal, enhancer-enriched sites undergoes TET2-driven demethylation and activation. Among these, we identified an AGO2 myeloid-specific intragenic enhancer that is frequently hypermethylated in TET2-mutant AML patients. AGO2 expression stratifies patient survival, and AGO2 depletion abrogates leukemic engraftment in vivo. These findings uncover a TET2-AGO2 regulatory axis that integrates epigenetic remodeling, 3D genome reorganization, and leukemic fitness, and they highlight AGO2 as a potential biomarker and therapeutic target in myeloid leukemia.

genomics↗

bioRxiv2024

Modulating immune cell fate and inflammation through CRISPR-mediated DNA methylation editing

DNA methylation is traditionally associated with gene silencing, but its causal relationship and role in shaping cell fate decisions still need to be fully elucidated. Here, we conducted a genome-wide analysis to investigate the relationship between DNA methylation and gene expression at gene regulatory regions in human immune cells. By utilizing CRISPR-dCas9 DNA methylation editing tools, we successfully established a cause-and-effect relationship between the methylation levels of the promoter of the Interleukin1-receptor antagonist (IL1RN) gene and its expression. Notably, we observed that modifying the DNA methylation status of the IL1RN promoter is sufficient to alter the acquisition of the human myeloid cell fate and change the cellular response to inflammatory stimuli, resulting in abnormal cytokine release and distinctive capacity to support cancer growth.

genomics↗

bioRxiv2023

The Interferon gamma Pathway Enhances Pluripotency and X-Chromosome Reactivation in iPSC Reprogramming

Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) requires activation of the pluripotency network and resetting of the epigenome by erasing the epigenetic memory of the somatic state. In female mouse cells, a critical epigenetic reprogramming step is the reactivation of the inactive X chromosome. Despite its importance, a systematic understanding of the regulatory networks linking pluripotency and X-reactivation is missing. Here we reveal the pathways important for iPSC reprogramming and X-reactivation using a genome-wide CRISPR screen. In particular, we discover that activation of the interferon {gamma} (IFN{gamma}) pathway early during reprogramming accelerates pluripotency acquisition and X-reactivation. IFN{gamma} stimulates STAT3 signaling and the pluripotency network and leads to enhanced TET-mediated DNA demethylation, which consequently boosts X-reactivation. We therefore gain a mechanistic understanding of the role of IFN{gamma} in reprogramming and X-reactivation and provide a comprehensive resource of the molecular networks involved in these processes.

genetics↗