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Definition of regulatory network elements for T cell development by perturbation analysis with PU.1 and GATA-3
- Source :
- Developmental biology. 246(1)
- Publication Year :
- 2002
-
Abstract
- PU.1 and GATA-3 are transcription factors that are required for development of T cell progenitors from the earliest stages. Neither one is a simple positive regulator for T lineage specification, however. When expressed at elevated levels at early stages of T cell development, each of these transcription factors blocks T cell development within a different, characteristic time window, with GATA-3 overexpression initially inhibiting at an earlier stage than PU.1. These perturbations are each associated with a distinct spectrum of changes in the regulation of genes needed for T cell development. Both transcription factors can interfere with expression of the Rag-1 and Rag-2 recombinases, while GATA-3 notably blocks PU.1 and IL-7Rα expression, and PU.1 reduces expression of HES-1 and c-Myb. A first-draft assembly of the regulatory targets of these two factors is presented as a provisional gene network. The target genes identified here provide insight into the basis of the effects of GATA-3 or PU.1 overexpression and into the regulatory changes that distinguish the developmental time windows for these effects.
- Subjects :
- T cell
retroviral transduction
T-Lymphocytes
Gene regulatory network
Regulator
pre-TCR
GATA3 Transcription Factor
Biology
GATA-3
03 medical and health sciences
Mice
0302 clinical medicine
Time windows
Proto-Oncogene Proteins
Genes, Regulator
Recombinase
medicine
Animals
Ets family
Cell Lineage
RNA, Messenger
Progenitor cell
Gene
Transcription factor
Molecular Biology
030304 developmental biology
DNA Primers
Genetics
Mice, Knockout
0303 health sciences
Base Sequence
Reverse Transcriptase Polymerase Chain Reaction
T cell development
PU.1
Cell Biology
fetal thymus organ culture
Cell biology
DNA-Binding Proteins
medicine.anatomical_structure
HES-1
c-Myb
IL-7 receptor
Trans-Activators
030215 immunology
Developmental Biology
Subjects
Details
- ISSN :
- 00121606
- Volume :
- 246
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Developmental biology
- Accession number :
- edsair.doi.dedup.....06b4e01439b689cee0e46bbbf1e2597f