Genome-wide identification of transcriptional enhancers During human placental development and association with function, differentiation, and disease

Biol Reprod. 2023 Sep 11:ioad119. doi: 10.1093/biolre/ioad119. Online ahead of print.ABSTRACTThe placenta is a dynamic organ which must perform a remarkable variety of functions during its relatively short existence in order to support a developing fetus. These functions include nutrient delivery, gas exchange, waste removal, hormone production, and immune barrier functions. Proper placenta development and function is critical for healthy pregnancy outcomes, but the underlying genomic regulatory events that control this process remain largely unknown. We hypothesized that mapping sites of transcriptional enhancer activity and associated changes in gene expression across gestation in human placenta tissue would identify genomic loci and predicted transcription factor activity related to critical placenta functions. We used a suite of genomic assays (i.e. RNA-seq, PRO-seq, ChIP-seq) and computational pipelines to identify a set of >20,000 enhancers which are active at various time points in gestation. Changes in the activity of these enhancers correlate with changes in gene expression. In addition, some of these enhancers encode risk for adverse pregnancy outcomes. We further show that integrating enhancer activity, transcription factor motif analysis, and transcription factor expression can identify distinct sets of transcription factors predicted to be more active either in early pregnancy or at term. Knockdown of selected identified transcription factors in a trophoblast ...
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Source Type: research