Transcriptomics,Multiomics

Dataset Information

4

Transcription profiling by high throughput sequencing in PER2 mutant of human endometrial stromal cells


ABSTRACT: Implantation is dependent on synchronized interactions between the conceptus and surrounding decidual cells but the involvement of clock genes in this process is not well understood. Circadian oscillations are predicated on transcriptional-translational feedback loops, which balance the activities of the transcriptional activators CLOCK and BMAL1 and repressors encoded by PER and CRY genes. Here we show that loss of PER2 expression silences circadian oscillations in decidualizing human endometrial stromal cells (HESCs). Downregulation was preceded by reduced CLOCK binding to a noncanonical E-box enhancer in the PER2 promoter and occurred between 12 - 24 h after exposure to a deciduogenic stimulus. RNA sequencing revealed that premature inhibition of PER2 by siRNA knockdown leads to a grossly disorganised decidual response. Gene ontology analysis highlighted a preponderance of cell cycle regulators amongst the 1,121 genes perturbed upon PER2 knockdown. Congruently, PER2 inhibition abrogated mitotic expansion of differentiating HESCs by inducing cell cycle block at G2/M. Analysis of mid-luteal endometrial biopsies revealed an inverse correlation between PER2 transcript levels and the number of miscarriages in women suffering reproductive failure. Thus, PER2 synchronizes mitotic expansion of HESCs with a periodic decidual gene expression; uncoupling of these events may cause persistent pregnancy failure. Endometrial mRNA profiles of paired control (siRNA-NT) and siRNA-PER2 were generated by deep sequencing, in triplicate using Illumina

REANALYSIS of: E-GEOD-62854

ORGANISM(S): Homo sapiens  

PROVIDER: E-GEOD-62854 | ExpressionAtlas | 2016-04-22

REPOSITORIES: ExpressionAtlas

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Publications

The clock protein period 2 synchronizes mitotic expansion and decidual transformation of human endometrial stromal cells.

Muter Joanne J   Lucas Emma S ES   Chan Yi-Wah YW   Brighton Paul J PJ   Moore Jonathan D JD   Lacey Lauren L   Quenby Siobhan S   Lam Eric W-F EW   Brosens Jan J JJ  

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20150108 4


Implantation requires coordinated interactions between the conceptus and surrounding decidual cells, but the involvement of clock genes in this process is incompletely understood. Circadian oscillations are predicated on transcriptional-translational feedback loops, which balance the activities of the transcriptional activators CLOCK (circadian locomotor output cycles kaput) and brain muscle arnt-like 1 and repressors encoded by PER (Period) and Cryptochrome genes. We show that loss of PER2 expr  ...[more]

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