The technical advances achieved during the last 20 years have shown that the spatial organization of chromatin is a very dynamic process with a deep influence on the control of gene expression. During interphase, the genome organizes into hierarchical domains at different genomic scales.
At the highest order of the nuclear architecture, chromosomes preferentially occupy regions called chromosome territories. At this scale, gene expression is influenced by relative positioning to specialized regions within the nucleus, like the repressive lamina-associating domains (LADs) or the transcriptional active nuclear speckles. At a sub-chromosomal level, chromosomes segregate into two mutually exclusive chromatin varieties, A and B. These compartments are genomic environments associated with active (A) and repressive (B) epigenetic marks that contribute to determining the transcriptional behavior of the genes encoded within these regions. At the sub-megabase scale, chromatin is organized into regions of preferential intradomain interaction called topologically associating domains (TADs). Formation of these structures promotes interaction between loci within the TAD, ensuring the appropriate cross-talk between enhancers and promoters and facilitating gene co-regulation. At the most local level of organization, chromatin is organized into loops, involved in the formation of chromatin microenvironments and the direct control of transcription by mediating enhancer-promoter interactions.
To study how these structural features and the rest of the epigenetic factors participate in the establishment of healthy and pathological transcriptional landscapes, our group combines the use of high-throughput protocols (like Hi-C, ATAC-seq, ChIP, RRBS and RNA-seq) with microscopy techniques and animal models that resemble human cardiac disease.
Projects
Examination of the effect that cardiac stressors exert on chromatin topology. Heart failure is highly associated with comorbidities promoted by external factors like diet, smoking, or lack of exercise. In this project, we are studying how these stressors participate in the setting of cardiac pathology by reorganizing cardiac chromatin structure.
Development of novel approaches to treat cardiac disease through modulation of chromatin structure. Different epigenetic strategies have been used to treat cardiac disease. However, modification of genomic structure has never been tested. This work aims to develop novel approaches to treat and prevent cardiac pathology based on the direct 3D remodeling of the cardiac chromatin.
Integrative analysis of cardiac epigenetics in human heart failure. Cardiac disease is a costly condition affecting millions of people worldwide. This study uses human cardiac tissue to collectively analyze the influence of epigenetic factors (DNA methylation, histone marks, chromatin accessibility, and high-order chromatin structure) in triggering the onset of heart failure.
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