Abstract
GATA factors interact with simple DNA motifs (WGATAR) to regulate
critical processes, including hematopoiesis, but very few WGATAR
motifs are occupied in genomes. Given the rudimentary knowledge of
mechanisms underlying this restriction and how GATA factors establish
genetic networks, we used ChIP-seq to define GATA-1 and GATA-2 occupancy
genome-wide in erythroid cells. Coupled with genetic complementation
analysis and transcriptional profiling, these studies revealed a
rich collection of targets containing a characteristic binding motif
of greater complexity than WGATAR. GATA factors occupied loci encoding
multiple components of the Scl/TAL1 complex, a master regulator of
hematopoiesis and leukemogenic target. Mechanistic analyses provided
evidence for crossregulatory and autoregulatory interactions among
components of this complex, including GATA-2 induction of the hematopoietic
corepressor ETO-2 and an ETO-2-negative autoregulatory loop. These
results establish fundamental principles underlying GATA factor mechanisms
in chromatin and illustrate a complex network of considerable importance
for the control of hematopoiesis.
- analysis,
- animals;
- basic
- biology;
- cells;
- chromatin
- chromatin,
- complexes,
- computational
- dna
- expression
- factor,
- factors,
- gata1
- gata2
- gene
- genetic
- genetics;
- genome,
- helix-loop-helix
- hematopoietic
- homeostasis;
- human,
- humans;
- immunoprecipitation;
- k562
- leukemia,
- loci;
- metabolism/pathology;
- metabolism;
- mice;
- multiprotein
- nuclear
- profiling;
- proteins,
- proto-oncogene
- sequence
- system,
- transcription
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