TY - JOUR
T1 - Relationships between PROMPT and gene expression
AU - Lloret-Llinares, Marta
AU - Mapendano, Christophe K
AU - Martlev, Lasse H
AU - Lykke-Andersen, Søren
AU - Jensen, Torben Heick
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Apoptosis Regulatory Proteins
KW - Cathepsin Z
KW - DNA Methylation
KW - Exosomes
KW - Gene Expression
KW - HeLa Cells
KW - Humans
KW - Promoter Regions, Genetic
KW - RNA Stability
KW - RNA, Antisense
KW - TATA-Box Binding Protein
KW - Transcription Factor TFIIB
KW - Transcription, Genetic
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1080/15476286.2015.1109769
DO - 10.1080/15476286.2015.1109769
M3 - Letter
C2 - 26574648
SN - 1547-6286
VL - 13
SP - 6
EP - 14
JO - RNA Biology
JF - RNA Biology
IS - 1
ER -