Definition of regulatory network elements for T cell development by perturbation analysis with PU.1 and GATA-3.
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-7Ralpha 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.
Anderson
Michele K
MK
Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Hernandez-Hoyos
Gabriela
G
Dionne
Christopher J
CJ
Arias
Alexandra M
AM
Chen
Dan
D
Rothenberg
Ellen V
EV
D000818:Animals; D001483:Base Sequence; D019070:Cell Lineage / Q000502:physiology*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D050990:GATA3 Transcription Factor; D005809:Genes, Regulator; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D000099232:Proto-Oncogene Protein Spi-1
D017931:DNA Primers; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C494748:Gata3 protein, mouse