We study the interplay between intra- and inter-chromosomal genome architecture in gene expression
Ongoing Projects
We are building genomic methods and analytical pipelines to study the functional role of inter-chromosomal (trans) interactions in RNA biogenesis
We are probing chromatin structure/function dynamics using super-resolution live microscopy
We are using the TTN locus as a gene model to study the hierarchical relationships between trans-acting chromatin regulators (i.e. architectural proteins and transcription factors), changes in chromatin architecture, and gene expression outputs
We are building genomic methods and analytical pipelines to study the functional role of inter-chromosomal (trans) interactions in RNA biogenesis
We are probing chromatin structure/function dynamics using super-resolution live microscopy
We are using the TTN locus as a gene model to study the hierarchical relationships between trans-acting chromatin regulators (i.e. architectural proteins and transcription factors), changes in chromatin architecture, and gene expression outputs
Earlier Contributions
While studying human cardiogenesis and disease we made the following general conclusions on chromatin biology: (1) changes in A/B compartmentalization correlate with gene expression dynamics during differentiation, particularly for large and lineage-specific genes which transition from the B to A compartment; (2) efficient segregation of alternative lineage loci into the B compartment requires of the formation of Lamin Associated Domains (LADs); (3) 3D chromatin reorganization correlates with changes in chromatin accessibility and dynamic binding of trans-acting regulators, such as CTCF and lineage-specific master transcriptional regulators; (4) inter-chromosomal (trans) interactions increase during differentiation and contribute to the control of gene expression, for instance by creating RNA splicing factories. Based on this last pivotal finding, we developed a testable hypothesis for the interplay of RNA biogenesis and inter-chromosomal structure
We clarified the molecular mechanisms by which the Activin/Nodal/TGFβ-SMAD2/3 pathway controls early cell fate decisions in hPSCs. SMAD2/3 is canonically regarded as a transcription factor, but how this protein regulates complex gene expression networks in hPSCs was at the time only poorly understood. In a first study we demonstrated that TGFβ orchestrates the pluripotent state in vitro and in vivo by shaping the H3K4me3 epigenetic landscape via SMAD2/3, the pluripotency factor NANOG, and the MLL/SET1A enzymatic complexes. In a second study, by means of a large-scale proteomic screening we revealed that SMAD2/3 interacts not only with transcriptional and epigenetic cofactors, but also with several complexes involved in functions ranging from DNA repair, mRNA biogenesis, and mRNA modification. We explored this unexpected finding and demonstrated that TGFβ controls the stability of key pluripotency genes by promoting deposition of the epitranscriptome mark N6-methlyadeonsine (m6A) through the interaction of SMAD2/3 with the m6A methyltransferase complex. This study was the first report mechanistically linking extracellular signalling to epitranscriptomic modifications. More in general, this work revealed the multifaceted function of TGFβ signalling, which we anticipate having implications in several other biological contexts.
While studying human cardiogenesis and disease we made the following general conclusions on chromatin biology: (1) changes in A/B compartmentalization correlate with gene expression dynamics during differentiation, particularly for large and lineage-specific genes which transition from the B to A compartment; (2) efficient segregation of alternative lineage loci into the B compartment requires of the formation of Lamin Associated Domains (LADs); (3) 3D chromatin reorganization correlates with changes in chromatin accessibility and dynamic binding of trans-acting regulators, such as CTCF and lineage-specific master transcriptional regulators; (4) inter-chromosomal (trans) interactions increase during differentiation and contribute to the control of gene expression, for instance by creating RNA splicing factories. Based on this last pivotal finding, we developed a testable hypothesis for the interplay of RNA biogenesis and inter-chromosomal structure
We clarified the molecular mechanisms by which the Activin/Nodal/TGFβ-SMAD2/3 pathway controls early cell fate decisions in hPSCs. SMAD2/3 is canonically regarded as a transcription factor, but how this protein regulates complex gene expression networks in hPSCs was at the time only poorly understood. In a first study we demonstrated that TGFβ orchestrates the pluripotent state in vitro and in vivo by shaping the H3K4me3 epigenetic landscape via SMAD2/3, the pluripotency factor NANOG, and the MLL/SET1A enzymatic complexes. In a second study, by means of a large-scale proteomic screening we revealed that SMAD2/3 interacts not only with transcriptional and epigenetic cofactors, but also with several complexes involved in functions ranging from DNA repair, mRNA biogenesis, and mRNA modification. We explored this unexpected finding and demonstrated that TGFβ controls the stability of key pluripotency genes by promoting deposition of the epitranscriptome mark N6-methlyadeonsine (m6A) through the interaction of SMAD2/3 with the m6A methyltransferase complex. This study was the first report mechanistically linking extracellular signalling to epitranscriptomic modifications. More in general, this work revealed the multifaceted function of TGFβ signalling, which we anticipate having implications in several other biological contexts.