GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:12493738

From GONUTS
Jump to: navigation, search
Citation

Funato, N, Ohyama, K, Kuroda, T and Nakamura, M (2003) Basic helix-loop-helix transcription factor epicardin/capsulin/Pod-1 suppresses differentiation by negative regulation of transcription. J. Biol. Chem. 278:7486-93

Abstract

Epicardin/capsulin/Pod-1, expressed in skeletal myoblasts within brachial arches and in the condensing mesenchyme, is a member of the basic helix-loop-helix (bHLH) transcription factor family that is involved in various cell differentiation processes. In this study, we examined the functional properties of epicardin/capsulin/Pod-1 in differentiation. The yeast and mammalian two-hybrid systems showed physical associations between epicardin/capsulin/Pod-1 and E2A, both of which were present in the nuclei. The bHLH domains mediated this association. Ectopic expression of epicardin/capsulin/Pod-1 inhibited E2A-dependent activation of the exogenous and endogenous expression of the cyclin-dependent kinase inhibitor, p21(WAF1/Cip1) gene, and the muscle creatine kinase gene that encodes the predominant creatine kinase isoform expressed in mammalian skeletal muscle. Transfection with epicardin/capsulin/Pod-1 small interfering RNA abolished the epicardin/capsulin/Pod-1-mediated suppression of E12-dependent activation of the p21 promoter. Chromatin immunoprecipitation assay showed that epicardin/capsulin/Pod-1 was physically associated with the muscle creatine kinase promoter in vivo. Moreover, terminal differentiation of C2C12 myoblasts was inhibited by exogenous introduction of epicardin/capsulin/Pod-1. These inhibitory functions of epicardin/capsulin/Pod-1 closely resemble those of the bHLH inhibitor Twist protein. These results indicate that epicardin/capsulin/Pod-1 functions as a negative regulator of differentiation of myoblasts through transcription in at least two distinct steps, cell growth arrest and lineage-specific differentiation.

Links

PubMed Online version:10.1074/jbc.M212248200

Keywords

Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation; Cell Line; Cell Lineage; Cell Nucleus/metabolism; Chromatin/metabolism; Cyclin-Dependent Kinase Inhibitor p21; Cyclins/metabolism; Humans; Immunoblotting; Luciferases/metabolism; Mice; Microscopy, Fluorescence; Muscles/cytology; Plasmids/metabolism; Precipitin Tests; Promoter Regions, Genetic; Protein Binding; RNA, Small Interfering/metabolism; Transcription Factors/physiology; Transcription, Genetic; Transcriptional Activation; Transfection; Tumor Cells, Cultured; Two-Hybrid System Techniques

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:TCF21

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TCF21

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TCF21

enables

GO:0001227: DNA-binding transcription repressor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(UniProtKB:P38936)
  • occurs_at:(SO:0001952)

Seeded From UniProt

complete

HUMAN:TCF21

enables

GO:0043425: bHLH transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P15923

F

Seeded From UniProt

complete

HUMAN:TFE2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TFE2

enables

GO:0140297: DNA-binding transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O43680

F

Seeded From UniProt

complete

HUMAN:TFE2

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TFE2

enables

GO:0070491: repressing transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O43680

F

Seeded From UniProt

complete

See also

References

See Help:References for how to manage references in GONUTS.