Regulation of hematopoietic expression of the tumor suppressor gene WT1

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133833

Wu, W J; Patmasiriwat, P; Stellrecht, C M ^[1]

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1. M.D. Anderson Cancer Center, Houston, TX (United States); and others

Understanding the regulation of WT1 in the hematopoietic system is important since this gene is expressed in fetal spleen and immature leukemias and likely plays a role in hematopoiesis. Because WT1 is downregulated in differentiated leukemia cells and is upregulated in fetal spleen and immature leukemia cells, WT1 expression may be a marker for progenitor cells and useful for the identification of residual blast cells. Using a quantitative RT-PCR assay, we compared WT1 expression in leukemic and differentiating K562 cells. To determine the molecular mechanism for the modulation of WT1 expression, we have identified hematopoietic-specific regulatory elements and characterized their interactions with hematopoietic-specific transcription factors. We observed co-expression of WT1 and GATA-1 RNA in K562 cells and in mouse spleen, so we evaluated their potential interactions. We found that the activity of the 3{prime} WT1 enhancer is correlated with GATA-1 expression. We have demonstrated by footprint analysis and gel shift competition, as well as transactivation studies, that this functional activity is mediated via binding at a 3{prime} GATA binding site. Sequence analysis reveals additional hematopoietic elements within the 3{prime} enhancer and promoter. We have examined two non-consensus GATA binding sites 5{prime} of the WT1 minimal promoter and observed that GATA-1 can also transactivate the WT1 promoter. The transactivation of WT1 regulatory elements by GATA-1 implies that GATA-1, a hematopoietic transcription factor, may play a role in the regulation of WT1 during hematopoiesis. Elucidating the role of tumor suppressor genes such as WT1 in normal developmental processes will aid understanding their roles in the development of cancer.

• OSTI ID: 133833
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BLOOD FORMATION
DNA SEQUENCING
GENE REGULATION
GENE REPRESSORS
GENES
HEMATOPOIETIC SYSTEM
LEUKEMIA
ONCOGENIC TRANSFORMATIONS
POLYMERASE CHAIN REACTION
RNA
STRUCTURE-ACTIVITY RELATIONSHIPS
TRANSCRIPTION FACTORS