Skip to main content

Advertisement

SpringerLink
Log in

Identification of Novel cAMP Responsive Element Modulator (CREM) Isoforms Expressed by Osteoblasts

  • Laboratory Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

CREM, the cyclic adenosine monophosphate (cAMP) responsive element modulator, belongs to a multigene family of cAMP-responsive transcription factors. CREM encodes a variety of different isoforms by utilizing four promoters and a complex pattern of alternative messenger ribonucleic acid (mRNA) splicing. We showed previously that parathyroid hormone induces the CREM P2 promoter products known as ICER (inducible cAMP early repressor) in osteoblasts. Herein we report that osteoblasts also express at least 15 CREM transcripts initiated from the P1 promoter, including 7 novel transcripts that result from alternative splicing. It is of interest that we found that CREM-X contains both exon θ1, previously identified only in P3 promoter products, and a new exon termed L, which is located upstream of exon θ1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. D Cesare ParticleDe D Sassone-Corsi (2000) ArticleTitleTranscriptional regulation by cyclic AMP-responsive factors Prog Nucleic Acid Res Mol Biol 64 343–369 Occurrence Handle10697414

    PubMed  Google Scholar 

  2. NS Foulkes E Borrelli P Sassone-Corsi (1991) ArticleTitleCREM gene: use of alternative DNA-binding domains generates multiple antagonists of cAMP-induced transcription Cell 64 739–749 Occurrence Handle10.1016/0092-8674(91)90503-Q Occurrence Handle1847666

    Article  PubMed  Google Scholar 

  3. PB Daniel L Rohrbach JF Habener (2000) ArticleTitleNovel cyclic adenosine 3´,5´-monophosphate (cAMP) response element modulator theta isoforms expressed by two newly identified cAMP-responsive promoters active in the testis Endocrinology 141 3923–3930 Occurrence Handle10.1210/en.141.11.3923 Occurrence Handle11089521

    Article  PubMed  Google Scholar 

  4. N Herdegen JD Leah (1998) ArticleTitleInducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins Brain Res Brain Res Rev 28 370–490 Occurrence Handle10.1016/S0165-0173(98)00018-6 Occurrence Handle9858769

    Article  PubMed  Google Scholar 

  5. L Qin P Qiu L Wang X Li JT Swarthout P Soteropoulos P Tolias NC Partridge (2003) ArticleTitleGene expression profiles and transcription factors involved in parathyroid hormone signaling in osteoblasts revealed by microarray and bioinformatics J Biol Chem 278 19273–19731

    Google Scholar 

  6. JH Stehle NS Foulkes CA Molina V Simonneaux P Pevet P Sassone-Corsi (1993) ArticleTitleAdrenergic signals direct rhythmic expression of transcriptional represser CREM in the pineal gland Nature 365 314–320 Occurrence Handle10.1038/365314a0 Occurrence Handle8397338

    Article  PubMed  Google Scholar 

  7. B Gellersen R Kempf R Sandhowe GF Weinbauer R Behr (2002) ArticleTitleNovel leader exons of the cyclic adenosine 3´,5´-monophosphate response element modulator (CREM) gene, transcribed from promoters P3 and P4, are highly testis-specific in primates Mol Hum Reprod 8 965–976 Occurrence Handle10.1093/molehr/8.11.965 Occurrence Handle12397208

    Article  PubMed  Google Scholar 

  8. S Tetradis JM Nervina K Nemoto BE Kream (1998) ArticleTitleParathyroid hormone induces expression of the inducible cAMP early represser in osteoblastic MC3T3-E1 cells and mouse calvariae J Bone Miner Res 13 1846–1851 Occurrence Handle9844102

    PubMed  Google Scholar 

  9. JM Nervina S Tetradis YF Huang ND Harrison C Molina BE Kream (2003) ArticleTitleExpression of inducible cAMP early represser is coupled to the cAMP-protein kinase A signaling pathway in osteoblasts Bone 32 483–490 Occurrence Handle10.1016/S8756-3282(03)00056-5 Occurrence Handle12753864

    Article  PubMed  Google Scholar 

  10. JA Blendy KH Kaestner GF Weinbauer E Nieschlag G Schutz (1996) ArticleTitleSevere impairment of spermatogenesis in mice lacking the CREM gene Nature 380 162–165 Occurrence Handle10.1038/380162a0 Occurrence Handle8600391

    Article  PubMed  Google Scholar 

  11. PH Krebsbach JR Harrison AC Lichtler CO Woody DW Rowe BE Kream (1993) ArticleTitleTransgenic expression of COL1A1-chloramphenicol acetyltransferase fusion genes in bone: differential utilization of promoter elements in vivo and in cultured cells Mol Cell Biol 13 5168–5174 Occurrence Handle8355676

    PubMed  Google Scholar 

  12. BM Laoide NS Foulkes F Schlotter P Sassone-Corsi (1993) ArticleTitleThe functional versatility of CREM is determined by its modular structure EMBO J 12 1179–1191 Occurrence Handle8458330

    PubMed  Google Scholar 

  13. RP Groot Particlede P Sassone-Corsi (1993) ArticleTitleHormonal control of gene expression: multiplicity and versatility of cyclic adenosine 3´,5´-monophosphate-responsive nuclear regulators Mol Endocrinol 7 145–153 Occurrence Handle10.1210/me.7.2.145 Occurrence Handle8385737

    Article  PubMed  Google Scholar 

  14. B Gellersen R Kempf R Telgmann (1997) ArticleTitleHuman endometrial stromal cells express novel isoforms of the transcriptional modulator CREM and up-regulate ICER in the course of decidualization Mol Endocrinol 1 97–113 Occurrence Handle10.1210/me.11.1.97

    Article  Google Scholar 

  15. NS Foulkes B Mellstrom E Benusiglio P Sassone-Corsi (1992) ArticleTitleDevelopmental switch of CREM function during spermatogenesis: from antagonist to activator Nature 355 80–84 Occurrence Handle10.1038/355080a0 Occurrence Handle1370576

    Article  PubMed  Google Scholar 

  16. FU Muller P Boknik J Knapp J Neumann U Vahlensieck E Oetjen HH Scheld W Schmitz (1998) ArticleTitleIdentification and expression of a novel isoform of cAMP response element modulator in the human heart FASEB J 12 1191–1199 Occurrence Handle9737722

    PubMed  Google Scholar 

  17. B Mellstrom JR Naranjo NS Foulkes M Lafarga P Sassone-Corsi (1993) ArticleTitleTranscriptional response to cAMP in brain: specific distribution and induction of CREM antagonists Neuron 10 655–665 Occurrence Handle10.1016/0896-6273(93)90167-P Occurrence Handle8386526

    Article  PubMed  Google Scholar 

  18. D Cesare ParticleDe GM Fimia P Sassone-Corsi (1999) ArticleTitleSignaling routes to CREM and CREB: plasticity in transcriptional activation Trends Biochem Sci 24 281–285 Occurrence Handle10.1016/S0968-0004(99)01414-0 Occurrence Handle10390618

    Article  PubMed  Google Scholar 

  19. F Nantel L Monaco NS Foulkes D Masquilier M LeMeur K Henriksen A Dierich M Parvinen P Sassone-Corsi (1996) ArticleTitleSpermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice Nature 380 159–162 Occurrence Handle10.1038/380159a0 Occurrence Handle8600390

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant to B.E.K. (AR46542) from the National Institutes of Arthritis and Musculoskeletal Diseases (NIAMS) of the National Institutes of Health.

Author information

Authors and Affiliations

  1. Department of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA

    F. Liu & B. E. Kream

  2. Center for Molecular Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA

    Y.-F. Huang

Authors
  1. F. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y.-F. Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. E. Kream
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B. E. Kream.

Additional information

Nucleotide sequence data reported are available in GenBank database under the accession numbers: AY738715, AY738716, AY738717, AY738718, AY738719, AY738720, and AY738721.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, F., Huang, YF. & Kream, B.E. Identification of Novel cAMP Responsive Element Modulator (CREM) Isoforms Expressed by Osteoblasts. Calcif Tissue Int 77, 91–95 (2005). https://doi.org/10.1007/s00223-005-0003-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-005-0003-1

Keywords

Search

Navigation