Anthropoid primate-specific retroviral element THE1B controls expression of CRH in placenta and alters gestation length

PLoS Biology
Caitlin E Dunn-FletcherLouis J Muglia

Abstract

Pregnancy and parturition are intricately regulated to ensure successful reproductive outcomes. However, the factors that control gestational length in humans and other anthropoid primates remain poorly defined. Here, we show the endogenous retroviral long terminal repeat transposon-like human element 1B (THE1B) selectively controls placental expression of corticotropin-releasing hormone (CRH) that, in turn, influences gestational length and birth timing. Placental expression of CRH and subsequently prolonged gestational length were found in two independent strains of transgenic mice carrying a 180-kb human bacterial artificial chromosome (BAC) DNA that contained the full length of CRH and extended flanking regions, including THE1B. Restricted deletion of THE1B silenced placental CRH expression and normalized birth timing in these transgenic lines. Furthermore, we revealed an interaction at the 5' insertion site of THE1B with distal-less homeobox 3 (DLX3), a transcription factor expressed in placenta. Together, these findings suggest that retroviral insertion of THE1B into the anthropoid primate genome may have initiated expression of CRH in placental syncytiotrophoblasts via DLX3 and that this placental CRH is sufficient to al...Continue Reading

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Datasets Mentioned

BETA
GSE118289
GSE43520
GSE30611
GSE87726
GSE118284
GSE118283

Methods Mentioned

BETA
transgenic
PCR
RNA-seq
immunoprecipitation
electrophoretic mobility shift assay
dissection
cesarean section
biopsies
electrophoresis
ChIP-seq

Software Mentioned

RSEM
GraphPad Prism
Tophat2
LogOdds
bedtools
R Statistical Programming Language
UCSC Genome Browser
BodyMap
GraphPad
CisBP

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