Induction of ICER is superseded by smICER, challenging the impact of ICER under chronic beta-adrenergic stimulation.
Adrenergic beta-Agonists
/ pharmacology
Animals
Cardiomegaly
/ drug therapy
Cell Line
Cyclic AMP Response Element Modulator
/ genetics
Female
Gene Expression Regulation
/ drug effects
HEK293 Cells
Heart
/ drug effects
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Promoter Regions, Genetic
/ drug effects
Receptors, Adrenergic, beta
/ genetics
Transcription, Genetic
/ drug effects
cyclic AMP (cAMP)
gene regulation
heart
transcription factors
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
11
09
2019
revised:
30
03
2020
accepted:
21
04
2020
pubmed:
1
7
2020
medline:
26
2
2021
entrez:
1
7
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32602979
doi: 10.1096/fj.201902301RR
doi:
Substances chimiques
Adrenergic beta-Agonists
0
Crem protein, mouse
0
Receptors, Adrenergic, beta
0
Cyclic AMP Response Element Modulator
135844-64-3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11272-11291Informations de copyright
© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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