Dynamic transcriptome, accessible genome, and PGR cistrome profiles in the human myometrium.

Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J Subsets: MEDLINE

Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley
Original Publication: [Bethesda, Md.] : The Federation, [c1987-

Genome, Human* ; RNA-Seq* ; Transcriptome*; Muscle Proteins/*biosynthesis ; Myometrium/*metabolism ; Pregnancy/*metabolism ; Pregnancy Proteins/*biosynthesis; Adult ; Female ; Humans ; Muscle Proteins/genetics ; Pregnancy Proteins/genetics

The myometrium undergoes structural and functional remodeling during pregnancy. We hypothesize that myometrial genomic elements alter correspondingly in preparation for parturition. Human myometrial tissues from nonpregnant (NP) and term pregnant (TP) human subjects were examined by RNAseq, ATACseq, and PGR ChIPseq assays to profile transcriptome, assessible genome, and PGR occupancy. NP and TP specimens exhibit 2890 differentially expressed genes, reflecting an increase of metabolic, inflammatory, and PDGF signaling, among others, in adaptation to pregnancy. At the epigenome level, patterns of accessible genome change between NP and TP myometrium, leading to the altered enrichment of binding motifs for hormone and muscle regulators such as the progesterone receptor (PGR), Krüppel-like factors, and MEF2A transcription factors. PGR genome occupancy exhibits a significant difference between the two stages of the myometrium, concomitant with distinct transcriptomic profiles including genes such as ENO1, LHDA, and PLCL1 in the glycolytic and calcium signaling pathways. Over-representation of SRF, MYOD, and STAT binding motifs in PGR occupying sites further suggests interactions between PGR and major muscle regulators for myometrial gene expression. In conclusion, changes in accessible genome and PGR occupancy are part of the myometrial remodeling process and may serve as mechanisms to formulate the state-specific transcriptome profiles.
(© 2019 Federation of American Societies for Experimental Biology.)

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ZIA ES103311 United States ImNIH Intramural NIH HHS

Keywords: PGR cistrome; genome accessibility; human myometrial tissue; transcriptome

0 (Muscle Proteins)
0 (Pregnancy Proteins)

Date Created: 20200108 Date Completed: 20200928 Latest Revision: 20230519

20240829

PMC10189786

10.1096/fj.201902654R

31908010