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FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1
- Source :
- Journal of cell biology, 164(2), 175-184. Rockefeller University Press, Journal of Cell Biology, 164(2), 175-184. ROCKEFELLER UNIV PRESS, Journal of Cell Biology, 164, 175-184. Rockefeller University Press, The Journal of Cell Biology
- Publication Year :
- 2004
- Publisher :
- ROCKEFELLER UNIV PRESS, 2004.
-
Abstract
- Erythropoiesis requires tight control of expansion, maturation, and survival of erythroid progenitors. Because activation of phosphatidylinositol-3-kinase (PI3K) is required for erythropoietin/stem cell factor–induced expansion of erythroid progenitors, we examined the role of the PI3K-controlled Forkhead box, class O (FoxO) subfamily of Forkhead transcription factors. FoxO3a expression and nuclear accumulation increased during erythroid differentiation, whereas untimely induction of FoxO3a activity accelerated differentiation of erythroid progenitors to erythrocytes. We identified B cell translocation gene 1 (BTG1)/antiproliferative protein 2 as a FoxO3a target gene in erythroid progenitors. Promoter studies indicated BTG1 as a direct target of FoxO3a. Expression of BTG1 in primary mouse bone marrow cells blocked the outgrowth of erythroid colonies, which required a domain of BTG1 that binds protein arginine methyl transferase 1. During erythroid differentiation, increased arginine methylation coincided with BTG1 expression. Concordantly, inhibition of methyl transferase activity blocked erythroid maturation without affecting expansion of progenitor cells. We propose FoxO3a-controlled expression of BTG1 and subsequent regulation of protein arginine methyl transferase activity as a novel mechanism controlling erythroid expansion and differentiation.
- Subjects :
- Protein-Arginine N-Methyltransferases
Arginine
PRMT1
Cellular differentiation
MOLECULAR ANALYSIS
FORKHEAD TRANSCRIPTION FACTOR
Polymerase Chain Reaction
Mice
Genes, Reporter
erythropoiesis
Forkhead transcription factors
protein arginine methylation
cDNA microarray
hemic and lymphatic diseases
Chlorocebus aethiops
FACTOR FKHR-L1
Cloning, Molecular
STEM-CELL FACTOR
Luciferases
Promoter Regions, Genetic
Cells, Cultured
Oligonucleotide Array Sequence Analysis
Forkhead Box Protein O3
Cell Differentiation
3T3 Cells
Methylation
Neoplasm Proteins
APOPTOSIS
COS Cells
Erythropoiesis
PHOSPHATIDYLINOSITOL 3-KINASE
EXPRESSION
KINASE-B
Molecular Sequence Data
FACTOR AFX
Biology
Article
Cell Line
Animals
Humans
Progenitor cell
Transcription factor
DNA Primers
Base Sequence
Activator (genetics)
Cell Biology
Hematopoietic Stem Cells
Molecular biology
Enzyme Activation
N-METHYLTRANSFERASE
BTG1
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 15408140 and 00219525
- Volume :
- 164
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- The Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....a31c921c5071903360223b747ebba222