PT  - JOURNAL ARTICLE
AU  - Leonor Rib
AU  - Dominic Villeneuve
AU  - Viviane Praz
AU  - Nouria Hernandez
AU  - Nicolas Guex
AU  - Winship Herr
AU  - CycliX Consortium
TI  - Cycles of gene expression and genome response during mammalian tissue regeneration
AID  - 10.1101/309989
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 309989
4099  - http://biorxiv.org/content/early/2018/04/28/309989.short
4100  - http://biorxiv.org/content/early/2018/04/28/309989.full
AB  - Background Compensatory liver hyperplasia — or regeneration — induced by two-thirds partial hepatectomy (PH) permits the study of synchronized activation of mammalian gene expression, particularly in relation to cell proliferation. Here, we measured genomic transcriptional responses and mRNA accumulation changes after PH and sham surgeries.Results During the first 10–20 hours, the PH- and sham-surgery responses were very similar, including parallel early activation of cell-division-cycle genes. After 20 hours, however, whereas post-PH livers continued with a robust and coordinate cell-division-cycle gene-expression response before returning to the resting state by one week, sham-surgery livers returned directly to a resting gene-expression state. Localization of RNA polymerase II (Pol II), and trimethylated histone H3 lysine 4 (H3K4me3) and 36 (H3K36me3) on genes dormant in the resting liver and activated during the PH response revealed a general de novo promoter Pol II recruitment and H3K4me3 increase during the early 10–20 hour phase followed by Pol II elongation and H3K36me3 accumulation in gene bodies during the later proliferation phase. H3K36me3, generally appearing at the first-internal exon, was preceded 5′ by H3K36me2; 3′ of the first-internal exon, in about half of genes H3K36me3 predominated and in the other half H3K36me2 and H3K36me3 co-existed. Further, we observed some unusual gene profiles with abundant Pol II but little evident H3K4me3 or H3K36me3 modification, indicating that these modifications are neither universal nor essential partners to Pol II transcription.Conclusions PH and sham surgical procedures on mice reveal striking early post-operatory gene expression similarities followed by synchronized mRNA accumulation and epigenetic histone mark changes specific to PH.CControl sampleGOGene Ontology databaseH3Histone 3H3K4me3trimethylated histone H3 lysine 4H3K36me3trimethylated histone H3 lysine 36H3K36me2dimethylated histone H3 lysine 36HDLHigh-density lipoprotein; mRNA: Messenger RNAPAMPartitioning Around Medoids clusteringPCPrincipal componentPCAPrincipal component analysisPHPartial hepatectomyPol IIRNA polymerase IIRNA-Sequltra-high-throughput RNA-sequencingRNA-Sequltra-high-throughput DNA-sequencingRPKMReads per Kb of transcript per million mapped readsSSham surgeriesSaaSerum amyloid ATSSTranscriptional start siteTUTranscription UnitXExcised liver hepatectomyZTZeitgeber Time