Induction of ICER is superseded by smICER, challenging the impact of ICER under chronic beta-adrenergic stimulation

Matthias D. Seidl; Benedikt Fels; Daniel Kranick; Alexandra Sternberg; Kristina Grimm; Frank T. Stümpel; Florentina Pluteanu; Jan S. Schulte; Alexander Heinick; Nobuhiko Kojima; Shogo Endo; Andreas Huge; Monika Stoll; Frank U. Müller

doi:10.1096/fj.201902301RR

Induction of ICER is superseded by smICER, challenging the impact of ICER under chronic beta-adrenergic stimulation

Matthias D. Seidl^*, Benedikt Fels, Daniel Kranick, Alexandra Sternberg, Kristina Grimm, Frank T. Stümpel, Florentina Pluteanu, Jan S. Schulte, Alexander Heinick, Nobuhiko Kojima, Shogo Endo, Andreas Huge, Monika Stoll, Frank U. Müller

^*Corresponding author for this work

Institute of Physiology

1 Citation (Scopus)

Abstract

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.

Original language	English
Journal	FASEB Journal
Volume	34
Issue number	8
Pages (from-to)	11272-11291
Number of pages	20
ISSN	0892-6638
DOIs	https://doi.org/10.1096/fj.201902301RR
Publication status	Published - 01.08.2020

Funding

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).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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10.1096/fj.201902301RR

Cite this

Seidl, M. D., Fels, B., Kranick, D., Sternberg, A., Grimm, K., Stümpel, F. T., Pluteanu, F., Schulte, J. S., Heinick, A., Kojima, N., Endo, S., Huge, A., Stoll, M., & Müller, F. U. (2020). Induction of ICER is superseded by smICER, challenging the impact of ICER under chronic beta-adrenergic stimulation. FASEB Journal, 34(8), 11272-11291. https://doi.org/10.1096/fj.201902301RR

@article{c45f28c44e1b40e3a538c9593afef671,

title = "Induction of ICER is superseded by smICER, challenging the impact of ICER under chronic beta-adrenergic stimulation",

abstract = "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.",

author = "Seidl, \{Matthias D.\} and Benedikt Fels and Daniel Kranick and Alexandra Sternberg and Kristina Grimm and St{\"u}mpel, \{Frank T.\} and Florentina Pluteanu and Schulte, \{Jan S.\} and Alexander Heinick and Nobuhiko Kojima and Shogo Endo and Andreas Huge and Monika Stoll and M{\"u}ller, \{Frank U.\}",

note = "Funding Information: We thank Nina Goda, Maria Schulik, Stefanie Triebel, and Melanie Vo{\ss} for excellent technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft (DFG Mu1376/11‐1 and Mu1376/11‐3). Publisher Copyright: {\textcopyright} 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.",

year = "2020",

month = aug,

day = "1",

doi = "10.1096/fj.201902301RR",

language = "English",

volume = "34",

pages = "11272--11291",

journal = "FASEB Journal",

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Seidl, MD, Fels, B, Kranick, D, Sternberg, A, Grimm, K, Stümpel, FT, Pluteanu, F, Schulte, JS, Heinick, A, Kojima, N, Endo, S, Huge, A, Stoll, M & Müller, FU 2020, 'Induction of ICER is superseded by smICER, challenging the impact of ICER under chronic beta-adrenergic stimulation', FASEB Journal, vol. 34, no. 8, pp. 11272-11291. https://doi.org/10.1096/fj.201902301RR

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 - https://www.scopus.com/pages/publications/85087205353

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 -

Induction of ICER is superseded by smICER, challenging the impact of ICER under chronic beta-adrenergic stimulation

Abstract

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