THE1B is a candidate enhancer for placenta-specific regulation of <i>CRH</i> and other genes.

(A) Comparative genomic alignment of 16 primates and 3 nonprimate mammals (UCSC Genome Browser, hg38, accessed June 14, 2017). LTR element THE1B (red bar) is present in anthropoid primates (red lines of phylogenetic tree) and absent in prosimians and nonprimate mammals. (B) Alignment of PCR-amplified transcript (Sequenced Transcript) and reads from human placental transcriptome precapture (RNA-seq) and postcapture (Capture-seq) for THE1B-containing transcripts. Sequenced fusion transcript found in human and rhesus macaque joins THE1B to CRH exon 1. This transcript is not found in pre- or postcapture RNA-seq; however, THE1B is transcribed. Raw data can be found at GEO accession number GSE118289. (C) Heat map of coregulation of THE1B-associated genes in placenta relative to other tissues. THE1B-associated genes are less coregulated, and thus more divergent in expression, between placenta and other tissues when compared to a group of randomly selected genes. Numerical values and their corresponding colors represent the odds ratio of observing the effect of relative coexpression between tissue pairs, generated by nonparametric tests separately between each pair of tissues as described by Pavlicev and colleagues [33]. (D) Upper right, higher percentage of human placenta–enriched genes, compared with all genes, are associated with THE1B. (P = 0.015 by binomial test.) Lower left, the log2fold gene expression between human and mouse of THE1B-associated human placenta–enriched genes. Raw data can be found at GEO accessions GSE118289 and GSE43520 (human placenta), GSE43520 (mouse placenta), and GSE30611 (other human tissues). Numerical data can be found in S1 Data. CRH, corticotropin-releasing hormone; Endometr. strom., endometrial stromal cells; GEO, Gene Expression Omnibus; LTR, long terminal repeat; RNA-seq, RNA sequencing; THE1B, transposon-like human element 1B; UCSC, University of California, Santa Cruz.