3D genome organization during human decidualization

ANT L; LE DILY, F; PANIZZO, S; VALLEJO, G; PISCIOTTANO, F; BEATO, M; SARAGÜETA, PATRICIA

Congreso; XI Argentine Congress of Bioinformatics and Computational Biology (XI CAB2C); 2021

Asociación Argentina de Bioinformática y Biología Computacional

With the advent of High throughput Chromosome Conformation Capture (Hi-C) analysis it has become possible to query the organization of the entire genome simultaneously at the sequence level trough the quantification of its interactions (Lieberman-Aiden et al., 2009). The resulting contact frequency maps are able to display self-associating domains formed by short-range interactions among contiguous segments of the genome and can be visualized as ?triangles? present at the diagonal of Hi-C heatmaps. Classically, these contact domains are called compartments and Topologically Associating Domains (TADs).Compartments are defined by Principal Component Analysis (PCA), normally using Hi-C data binned at 0.5-1.0 Mb resolution and, as a consequence, compartments are normally considered to be larger than 1 Mb in size. Compartments can contain sequences in an active (A) or silenced (B) transcriptional state and they interact with other compartments in the same state to give the plaid pattern observed in Hi-C heat-maps. On the other hand, neighbouring regions in separate compartmental domains interact less frequently and represent a compartmental switch or border. In this way, the compartmentalization of the genome creates both local compartmental domains and distant compartmental interactions. In consequence, the chromatin organization can play an important role in transcriptional regulation, for example creating a microenvironment where genes regulated by a transcription factor aggregate together to coordinate their expression, or insulating an enhancer from its target gene to downregulate it. Results:In this work we explore the dynamics of the chromatin landscape and the transcriptional reprograming during decidualization of tHESC cells, a trans-differentiation process inherent of the human stromal endometrial cells. Decidualization was induced by exposure to cAMP, E2 and either progesterone or the synthetic progestin R5020 and Hi-C and RNAseq assays were performed at 60 minutes, 3 and 6 days later. Implementing only a few basic packages we were able to create custom Python scripts to extract the information from the raw data of RNAseq and Hi-C that provides some insight into the mechanisms of genome 3D organization that takes place in this process.The PC1 values from the PCA of the Pearson correlation matrices were used to evaluate the global compartment reconfiguration, analysing correlation between different time points. The positive correlation (p-value