CHROMATIN SPATIAL ORGANIZATION DURING DECIDUALIZATION

ANT, LUCIANA; ERRAMOUSPE, JULIETA; LE DILY, FRANCOIS; BRUQUE, CARLOS DAVID; PANIZZO, SILVANA; VALLEJO, GRISELDA; PISCIOTTANO, FRANCISCO; BEATO, MIGUEL; SARAGÜETA, PATRICIA

Congreso; Reunión Conjunta SAIC - SAI - AAFE - NANOMED-AR; 2021

SAI-SAIC-AAFE-Nanomed

TITLE: CHROMATINSPATIAL ORGANIZATION DURING DECIDUALIZATIONAuthors:Luciana Ant1,Julieta Erramouspe1,Francois Le Dily2,Carlos David Bruque3,Silvana Panizzo1,Griselda Vallejo1,Francisco Pisciottano1,Miguel Beato2,Patricia Saragüeta1.1)Instituto de Biología y Medicina Experimental (IBYME-CONICET),Buenos Aires, Argentina.2)Centro de Regulación Genómica (CRG), Barcelona, Spain.3)Unidad de Conocimiento TraslacionalHospitalaria Patagónica, Hospital de Alta Complejidad SAMIC - ElCalafate, Provincia de Santa Cruz, Argentina.AbstractDecidualization is a process of endometrial trans-differentiationcrucial to sustain pregnancy. The events involved are regulated bysteroid hormones progesterone and estradiol (E2) via the ligandactivated transcription factors progesterone receptor (PR) andestrogen receptor (ER). Endometrial specific transcription is alsoregulated by HOXs and FOXO transcription factors. In this work weused High-throughput Chromosome Conformation Capture (Hi-C) toanalyze the changes in chromosome conformation organization andRNA-seq to explore changes in gene expression signatures at differenttime points of in vitro decidualization of human t-HESC cellline. Decidualization was induced by exposure to cAMP, E2 and eitherprogesterone or the synthetic progestin R5020. PGR and FOXO1, bothcrucial transcription factors in decidualization, showed >4 foldchange increase after 3 days of treatment. On the other hand thedecidualization markers, PRL and IGFBP1, both displayed >20 foldchange increase after 3 days. At day 1 the inflammatory signature wasdifferentially upregulated (FC>2, FDR<0.01) inhormone-dependent decidualization. This signature was changed at 3and 6 days, indicating distinct differential states. Globalchromosome conformation compartmentsanalysis through PCA of the Pearson correlation contact matricesshowed extensive remodelling of A and B compartments and positivecorrelation (p-value<0.01) between B to A compartment changes anddifferential gene expression during human decidualization. Inparticular, the Hox genes cluster showed dramatic changes in loopingconformation in this region and a correlation with changes indecidual specific genes expression after 6 days of treatment,indicating the increased interaction frequency between this clusterand the neighboring gene promoters. These results explore novel andglobal human endometrial enhancer-promoter relationships involve inhuman decidualization.p { margin-bottom: 0.1in; direction: ltr; line-height: 115%; text-align: left; orphans: 2; widows: 2 }