Hugo Sepúlveda, Ph.D.

Research

Our lab investigates how epigenetic mechanisms shape chromatin states to regulate gene expression and cellular identity. In eukaryotic cells, DNA is packaged into chromatin, a dynamic structure that not only enables genome compaction but also controls access to genetic information. A central question in our research is how epigenetic information is established, maintained, and modified to coordinate transcriptional programs in development and disease. We are currently focusing on the functional interplay between DNA methylation (5mC), DNA hydroxymethylation (5hmC), and protein O-GlcNAcylation, and how their associated enzymes DNMTs, TETs, and OGT cooperate to regulate chromatin conformation, transcription, and genome stability. These molecular pathways form interconnected regulatory networks that integrate biochemical signals to shape the epigenome and are altered in many human pathologies.

Although protein-coding genes represent a small fraction of the genome, most of it consists of repetitive elements, including transposable elements (TEs), which are typically silenced within heterochromatin. Loss of this silencing is a hallmark of multiple diseases, often leading to widespread TE activation and genomic instability. We seek to understand the mechanisms that maintain TE silencing and the molecular events that trigger their reactivation.  We are particularly interested in how specific TE families, such as LINEs and endogenous retroviruses (ERVs), can act as regulatory elements that influence gene expression and chromatin architecture.

By combining molecular biology, genomics, and computational approaches, we aim to uncover fundamental principles governing epigenome regulation in health and disease.