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p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) modulates co-operation between myocyte enhancer factor 2A (MEF2A) and thyroid hormone receptor-retinoid X receptor.

Thyroid hormone receptors (TRs) and members of the myocyte enhancer factor 2 (MEF2) family are involved in the regulation of muscle-specific gene expression during myogenesis. Physical interaction between these two factors is required to synergistically activate gene transcription. p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) interacting with transcription factors is able to increase their activity on target gene promoters. We investigated the role of p300 in regulating the TR-MEF2A complex. To this end, we mapped the regions of these proteins involved in physical interactions and we evaluated the expression of a chloramphenicol acetyltransferase (CAT) reporter gene in U2OS cells under control of the alpha-myosin heavy chain promoter containing the thyroid hormone response element (TRE). Our results suggested a role of p300/CBP in mediating the transactivation effects of the TR-retenoid X receptor (RxR)-MEF2A complex. Our findings showed that the same C-terminal portion of p300 binds the N-terminal domains of both TR and MEF2A, and our in vivo studies demonstrated that TR, MEF2A and p300 form a ternary complex. Moreover, by the use of CAT assays, we demonstrated that adenovirus E1A inhibits activation of transcription by TR-RxR-MEF2A-p300 but not by TR-RxR-MEF2A. Our data suggested that p300 can bind and modulate the activity of TR-RxR-MEF2A at TRE. In addition, it is speculated that p300 might modulate the activity of the TR-RxR-MEF2A complex by recruiting a hypothetical endogenous inhibitor which may act like adenovirus E1A.

Pubmed ID: 12371907

Authors

  • De Luca A
  • Severino A
  • De Paolis P
  • Cottone G
  • De Luca L
  • De Falco M
  • Porcellini A
  • Volpe M
  • Condorelli G

Journal

The Biochemical journal

Publication Data

February 1, 2003

Associated Grants

None

Mesh Terms

  • Animals
  • COS Cells
  • Cells, Cultured
  • Chloramphenicol O-Acetyltransferase
  • Chromatin
  • DNA-Binding Proteins
  • Electrophoretic Mobility Shift Assay
  • Humans
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • Myogenic Regulatory Factors
  • Nuclear Proteins
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Retinoid X Receptors
  • Trans-Activators
  • Transcription Factors