TY - JOUR
T1 - Induction of ICER is superseded by smICER, challenging the impact of ICER under chronic beta-adrenergic stimulation
AU - Seidl, Matthias D.
AU - Fels, Benedikt
AU - Kranick, Daniel
AU - Sternberg, Alexandra
AU - Grimm, Kristina
AU - Stümpel, Frank T.
AU - Pluteanu, Florentina
AU - Schulte, Jan S.
AU - Heinick, Alexander
AU - Kojima, Nobuhiko
AU - Endo, Shogo
AU - Huge, Andreas
AU - Stoll, Monika
AU - Müller, Frank U.
N1 - Funding Information:
We thank Nina Goda, Maria Schulik, Stefanie Triebel, and Melanie Voß for excellent technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft (DFG Mu1376/11‐1 and Mu1376/11‐3).
Publisher Copyright:
© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - ICER (inducible cAMP early repressor) isoforms are transcriptional repressors encoded by the Crem (cAMP responsive element modulator) gene. They were linked to the regulation of a multitude of cellular processes and pathophysiological mechanisms. Here, we show for the first time that two independent induction patterns for CREM repressor isoforms exist in the heart, namely for ICER and smICER (small ICER), which are induced in response to β-adrenergic stimulation in a transient- and saturation-like manner, respectively. This time-shifted induction pattern, driven by two internal promoters in the Crem gene, leads to the predominant transcription of smIcer after prolonged β-adrenergic stimulation. Using an ICER knockout mouse model with preserved smICER induction, we show that the transient-like induction of Icer itself has minor effects on gene regulation, cardiac hypertrophy or contractile function in the heart. We conclude that the functions previously linked to ICER may be rather attributed to smICER, also beyond the cardiac background.
AB - ICER (inducible cAMP early repressor) isoforms are transcriptional repressors encoded by the Crem (cAMP responsive element modulator) gene. They were linked to the regulation of a multitude of cellular processes and pathophysiological mechanisms. Here, we show for the first time that two independent induction patterns for CREM repressor isoforms exist in the heart, namely for ICER and smICER (small ICER), which are induced in response to β-adrenergic stimulation in a transient- and saturation-like manner, respectively. This time-shifted induction pattern, driven by two internal promoters in the Crem gene, leads to the predominant transcription of smIcer after prolonged β-adrenergic stimulation. Using an ICER knockout mouse model with preserved smICER induction, we show that the transient-like induction of Icer itself has minor effects on gene regulation, cardiac hypertrophy or contractile function in the heart. We conclude that the functions previously linked to ICER may be rather attributed to smICER, also beyond the cardiac background.
UR - http://www.scopus.com/inward/record.url?scp=85087205353&partnerID=8YFLogxK
U2 - 10.1096/fj.201902301RR
DO - 10.1096/fj.201902301RR
M3 - Journal articles
C2 - 32602979
AN - SCOPUS:85087205353
SN - 0892-6638
VL - 34
SP - 11272
EP - 11291
JO - FASEB Journal
JF - FASEB Journal
IS - 8
ER -
