title: Relationships between PROMPT and gene expression.
abstract: Most mammalian protein-coding gene promoters are divergent, yielding promoter upstream transcripts (PROMPTs) in the reverse direction from their conventionally produced mRNAs. PROMPTs are rapidly degraded by the RNA exosome rendering a general function of these molecules elusive. Yet, levels of certain PROMPTs are altered in stress conditions, like the DNA damage response (DDR), suggesting a possible regulatory role for at least a subset of these molecules. Here we manipulate PROMPT levels by either exosome depletion or UV treatment and analyze possible effects on their neighboring genes. For the CTSZ and DAP genes we find that TFIIB and TBP promoter binding decrease when PROMPTs accumulate. Moreover, DNA methylation increases concomitant with the recruitment of the DNA methyltransferase DNMT3B. Thus, although a correlation between increased PROMPT levels and decreased gene activity is generally absent, some promoters may have co-opted their divergent transcript production for regulatory purposes.
authors.affiliation: a Centre for mRNP Biogenesis and Metabolism , Department of Molecular Biology and Genetics, Aarhus University , DK-8000 , Aarhus , Denmark.|d Shared first authorship.
authors.forename: Marta
authors.initials: M
authors.lastname: Lloret-Llinares
authors.affiliation: a Centre for mRNP Biogenesis and Metabolism , Department of Molecular Biology and Genetics, Aarhus University , DK-8000 , Aarhus , Denmark.|b Present address; Emergency Department , Horsens Hospital , DK-8700 Horsens , Denmark.|d Shared first authorship.
authors.forename: Christophe K
authors.initials: CK
authors.lastname: Mapendano
authors.affiliation: a Centre for mRNP Biogenesis and Metabolism , Department of Molecular Biology and Genetics, Aarhus University , DK-8000 , Aarhus , Denmark.|c Present address: Seahorse Bioscience , Symbion , DK-2100 , Copenhagen , Denmark.
authors.forename: Lasse H
authors.initials: LH
authors.lastname: Martlev
authors.affiliation: a Centre for mRNP Biogenesis and Metabolism , Department of Molecular Biology and Genetics, Aarhus University , DK-8000 , Aarhus , Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Lykke-Andersen
authors.affiliation: a Centre for mRNP Biogenesis and Metabolism , Department of Molecular Biology and Genetics, Aarhus University , DK-8000 , Aarhus , Denmark.
authors.forename: Torben Heick
authors.initials: TH
authors.lastname: Jensen
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D056663:Cathepsin Z / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D055354:Exosomes / Q000378:metabolism*; D015870:Gene Expression / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic / Q000528:radiation effects; D020871:RNA Stability; D016372:RNA, Antisense / Q000737:chemistry / Q000378:metabolism*; D035181:TATA-Box Binding Protein / Q000378:metabolism; D035581:Transcription Factor TFIIB / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D051017:Apoptosis Regulatory Proteins; C091572:DAP protein, human; D016372:RNA, Antisense; D035181:TATA-Box Binding Protein; C509817:TBP protein, human; D035581:Transcription Factor TFIIB; C534182:CTSZ protein, human; D056663:Cathepsin Z
keywords: DNA damage response; DNA methylation; Divergent transcription; PROMPT; RNA exosome; RNASeq; mRNA