Project description:Histone acetyltransferases KAT2A and KAT2B are paralogs highly expressed in the intestinal epithelium, but their functions are not well understood. In this study, double knockout of murine Kat2 genes in the intestinal epithelium was lethal, resulting in diminished H3K9ac
expression, loss of stem cells, and robust activation of interferon signaling. Use of pharmacological agents and sterile organoid cultures indicated a cell-intrinsic double-stranded RNA trigger for interferon signaling. Acetyl-proteomics and dsRIP-seq were employed to interrogate the mechanism behind this response, which identified self-derived, mitochondria- encoded double-stranded RNA as the source of intrinsic interferon signaling. KAT2A and KAT2B therefore play an essential role in regulating mitochondrial functions as well as maintaining intestinal health.
Project description:Multiple HPV genotypes infection is frequently detected in HPV+ cervical lesions, however it is not well stablished how is the different viral interaction during the carcinogenic process. Here we carried out a comprehensive study to characterize the multiple HPV genome expression and integration by RNA-Seq analysis in 19 invasive cervical carcinomas with HPV coinfections. Analysis of tumoral DNA by a hybridization kit indicated multi-infection ranging from 2 to 6 different HPV genotypes, without a preferential species coinfection. The expression analysis showed that a single HPV genotype preferentially expressed its genome, might indicating a competition between the infecting virus. Finally, the search for HPV/human chimeric transcripts indicated integration from just one HPV in almost all samples, corroborating the expression findings.
Project description:To study the role of epigenetics and hormones on hematopoietic stem cell function, hematopoietic stem and progenitor (LSK) cells were sorted from E14.5 embryos of wild-type, DNMT3B7 hemizygous or DNMT3B7 homozygous genotype. The expression analysis was performed to provide information regarding the mechanism by which hormones regulate hematopoiesis. Hematopoietic stem and progenitor (LSK) cells from E14.5 murine embryonic fetal livers of wild-type, or DNMT3B7 transgenic genotypes were flow-sorted, and RNA isolated for expression analysis by RNA-Sequencing