Controlling Hematopoiesis through Sumoylation-Dependent Regulation of a GATA Factor

Hsiang Ying Lee, Kirby D. Johnson, Tohru Fujiwara, Meghan E. Boyer, Shin Il Kim, Emery H. Bresnick

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

GATA factors establish transcriptional networks that control fundamental developmental processes. Whereas the regulator of hematopoiesis GATA-1 is subject to multiple posttranslational modifications, how these modifications influence GATA-1 function at endogenous loci is unknown. We demonstrate that sumoylation of GATA-1 K137 promotes transcriptional activation only at target genes requiring the coregulator Friend of GATA-1 (FOG-1). A mutation of GATA-1 V205G that disrupts FOG-1 binding and K137 mutations yielded similar phenotypes, although sumoylation was FOG-1 independent, and FOG-1 binding did not require sumoylation. Both mutations dysregulated GATA-1 chromatin occupancy at select sites, FOG-1-dependent gene expression, and were rescued by tethering SUMO-1. While FOG-1- and SUMO-1-dependent genes migrated away from the nuclear periphery upon erythroid maturation, FOG-1- and SUMO-1-independent genes persisted at the periphery. These results illustrate a mechanism that controls trans-acting factor function in a locus-specific manner, and differentially regulated members of the target gene ensemble reside in distinct subnuclear compartments.

Original languageEnglish
Pages (from-to)984-995
Number of pages12
JournalMolecular Cell
Volume36
Issue number6
DOIs
Publication statusPublished - 2009 Dec 24
Externally publishedYes

Keywords

  • DEVBIO
  • DNA
  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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