IRF-2 Is Involved in Up-regulation of Nonmuscle Myosin Heavy Chain II-A Gene Expression during Phorbol Ester-induced Promyelocytic HL-60 Differentiation

Autor: Sachiyo Kawamoto, Myung-Chul Chung
Rok vydání: 2004
Předmět:
Transcription
Genetic
Response element
Biochemistry
Mice
Genes
Reporter
Transcription (biology)
Luciferases
Conserved Sequence
biology
Nonmuscle Myosin Type IIA
Cell Differentiation
Up-Regulation
DNA-Binding Proteins
Histone
Tetradecanoylphorbol Acetate
Plasmids
Protein Binding
Transcriptional Activation
Chromatin Immunoprecipitation
Cell type
Blotting
Western
Genetic Vectors
Molecular Sequence Data
Repressor
HL-60 Cells
Transfection
Cell Line
Sequence Homology
Nucleic Acid
Cell Adhesion
Animals
Humans
Molecular Biology
Gene
Reporter gene
Base Sequence
Models
Genetic
Macrophages
Cell Biology
Blotting
Northern
Molecular biology
Introns
Repressor Proteins
Gene Expression Regulation
NIH 3T3 Cells
biology.protein
Gene Deletion
Interferon Regulatory Factor-2
HeLa Cells
Transcription Factors
Interferon regulatory factors
Zdroj: Journal of Biological Chemistry. 279:56042-56052
ISSN: 0021-9258
DOI: 10.1074/jbc.m404791200
Popis: Transcription of the nonmuscle myosin heavy chain II-A (NMHC-A) gene is regulated by various factors, including cell type, proliferation and differentiation stage, and extracellular stimuli. We have identified an intronic region (designated 32kb-150), which is located 32 kb downstream of the transcription start sites in the human NMHC-A gene, as a transcriptional regulatory region. 32kb-150 contains an interferon-stimulated response element (ISRE). By using HeLa and NIH3T3 cells, in which NMHC-A is constitutively expressed, interferon regulatory factor (IRF)-2 was found to be the only major protein, among the IRF family proteins, that bound to the ISRE in 32kb-150 both in vitro and in intact cells. IRF-2, which is known to either repress or activate target gene expression, acts as a transcriptional activator in the context of the 32kb-150 reporter gene. The carboxyl-terminal basic region of IRF-2 serves as an activation domain in this context. This is in contrast to its acting as a repressor domain in the context of the synthetic core ISRE. Furthermore, after treatment of promyelocytic HL-60 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), which triggers differentiation into macrophages, both NMHC-A expression and IRF-2 expression were found to be up-regulated with a similar time course. TPA treatment leads to recruitment of IRF-2 to 32kb-150 of the endogenous NMHC-A gene and acetylation of the core histones surrounding this region. In addition, the ISRE in the 32kb-150 reporter gene recruits IRF-2 and mediates TPA-induced activation of a reporter gene in HL-60 cells. Together, these results indicate that IRF-2 contributes to transcriptional activation of the NMHC-A gene via 32kb-150 during TPA-induced differentiation of HL-60 cells.
Databáze: OpenAIRE
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