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Comparing the Affinity of GTPase-binding Proteins using Competition Assays
Published on: October 8, 2015
Context-dependent function of "GATA switch" sites in vivo
Jonathan W Snow1, Jennifer J Trowbridge, Kirby D Johnson
1Division of Hematology-Oncology, Children's Hospital Boston, Boston, MA, USA.
Blood
|March 15, 2011
Summary
Investigating cis-regulatory elements in vivo, this study found that a specific GATA motif region upstream of the Gata2 gene is crucial for maximal expression in hematopoietic stem cells and progenitors.
Area of Science:
- Developmental biology
- Gene regulation
- Hematopoiesis
Background:
- Master transcriptional regulators utilize dispersed cis-elements at target genes.
- In vivo function of cis-elements remains challenging to study.
- Gata2 is a critical hematopoietic transcription factor.
Purpose of the Study:
- To investigate the in vivo function of cis-regulatory elements controlling Gata2 expression.
- To determine the role of a GATA motif cluster at the -2.8 kb region upstream of the Gata2 gene.
Main Methods:
- Engineered mice lacking a cluster of GATA motifs at the -2.8 kb region upstream of the Gata2 locus.
- Assessed Gata2 expression in hematopoietic stem cells and progenitors.
Main Results:
- The -2.8 kb GATA motif region is essential for maximal Gata2 expression in hematopoietic stem cells and specific progenitors.
- This region is not required for Gata2 repression in terminally differentiating erythroid cells.
- Distinct GATA motif regions exhibit qualitatively different functions in vivo.
Conclusions:
- Dispersed cis-elements can have distinct roles in regulating gene expression during development.
- The -2.8 kb region plays a critical positive regulatory role in Gata2 expression during hematopoiesis.
- In vivo analysis of cis-element function is vital for understanding gene regulation.
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