Context-dependent GATA Factor Function

Wozniak, Ryan J.; Boyer, Meghan E.; Grass, Jeffrey A.; Lee, Youngsook; Bresnick, Emery H.

doi:10.1074/jbc.m700792200

Cited by 55 publications

(28 citation statements)

References 62 publications

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“…These studies along with our findings strongly indicate intrinsic differences among the Gata2 regulatory regions. These intrinsic differences, at least in part, are contributed by other tissuespecific transcription factors, which function in combination with GATA factors from the regulatory regions (54,55). Therefore, determining those factors in trophoblast cells is an area of further research.…”

Section: Discussionmentioning

confidence: 99%

Context-dependent Function of Regulatory Elements and a Switch in Chromatin Occupancy between GATA3 and GATA2 Regulate Gata2 Transcription during Trophoblast Differentiation

Ray

Dutta

Rumi

et al. 2009

Journal of Biological Chemistry

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GATA transcription factors are important regulators of tissue-specific gene expression during development. GATA2 and GATA3 have been implicated in the regulation of trophoblastspecific genes. However, the regulatory mechanisms of GATA2 expression in trophoblast cells are poorly understood. In this study, we demonstrate that Gata2 is transcriptionally induced during trophoblast giant cell-specific differentiation. Transcriptional induction is associated with displacement of GATA3-dependent nucleoprotein complexes by GATA2-dependent nucleoprotein complexes at two regulatory regions, the ؊3.9-and ؉9.5-kb regions, of the mouse Gata2 locus. Analyses with reporter genes showed that, in trophoblast cells, ؊3.9-and ؉9.5-kb regions function as transcriptional enhancers in GATA motif independent and dependent fashions, respectively. We also found that knockdown of GATA3 by RNA interference induces GATA2 in undifferentiated trophoblast cells. Interestingly, three other known GATA motif-dependent Gata2 regulatory elements, the ؊1.8-, ؊2.8-, and ؊77-kb regions, which are important to regulate Gata2 in hematopoietic cells are not occupied by GATA factors in trophoblast cells. These elements do not show any enhancer activity and also possess inaccessible chromatin structure in trophoblast cells indicating a contextdependent function. Our results indicate that GATA3 directly represses Gata2 in undifferentiated trophoblast cells, and a switch in chromatin occupancy between GATA3 and GATA2 (GATA3/GATA2 switch) induces transcription during trophoblast differentiation. We predict that this GATA3/GATA2 switch is an important mechanism for the transcriptional regulation of other trophoblast-specific genes.In the early mouse embryo, trophoectoderm overlaying the inner cell mass contains trophoblast stem (TS) 2 cells (1). During development, TS cells give rise to distinct highly differentiated trophoblast subtypes, which build the functional units of the organ, the placenta (2). Trophoblast cells are important for the anchorage of the embryo to the mother, for establishing a vascular connection for nutrient and gas transport to the embryo, and expression of hormones that are required for the successful progression of pregnancy (3). In rodents, multiple differentiated cell types can be derived from TS cells: trophoblast giant cells, spongiotrophoblast, syncytiotrophoblast, glycogen trophoblast cells, and invasive trophoblasts (2, 4). Trophoblast giant cells are characterized by endoreduplication and expression of members of the prolactin gene family. During pregnancy, these cells invade into the uterus and promote local and systemic adaptations in the mother that are necessary for embryonic growth and survival (2, 3). Differentiation of trophoblast giant cells occurs in a spatially and temporally highly organized manner and multiple transcription factors, including GATA2 and GATA3, have been implicated in the transcriptional regulation of trophoblast giant cell-specific gene expression (5-8).The GATA family of transcription factors, GAT...

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Section: Discussionmentioning

confidence: 99%

Context-dependent Function of Regulatory Elements and a Switch in Chromatin Occupancy between GATA3 and GATA2 Regulate Gata2 Transcription during Trophoblast Differentiation

Ray

Dutta

Rumi

et al. 2009

Journal of Biological Chemistry

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“…GATA-1 and GATA-2 occupy a small percentage of these composite elements in the genome (20,21). The ϩ9.5 site represents such a composite element, and its targeted deletion in the mouse revealed its requirement for embryogenesis, HSC generation in the AGM, and establishment of the HSPC compartment (9,17,22,55,85). In certain cases, Scl/TAL1 occupies GATA motif-containing GATA factor-bound chromatin sites lacking the E-box component of the composite element (70).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Determinants of Erythropoiesis: Role of the Histone Methyltransferase SetD8 in Promoting Erythroid Cell Maturation and Survival

DeVilbiss

Sanalkumar

Hall

et al. 2015

Molecular and Cellular Biology

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Erythropoiesis, in which committed progenitor cells generate millions of erythrocytes daily, involves dramatic changes in the chromatin structure and transcriptome of erythroblasts, prior to their enucleation. While the involvement of the master-regulatory transcription factors GATA binding protein 1 (GATA-1) and GATA-2 in this process is established, the mechanistic contributions of many chromatin-modifying/remodeling enzymes in red cell biology remain enigmatic. We demonstrated that SetD8, a histone methyltransferase that catalyzes monomethylation of histone H4 at lysine 20 (H4K20me1), is a context-dependent GATA-1 corepressor in erythroid cells. To determine whether SetD8 controls erythroid maturation and/or function, we used a small hairpin RNA (shRNA)-based loss-of-function strategy in a primary murine erythroblast culture system. In this system, SetD8 promoted erythroblast maturation and survival, and this did not involve upregulation of the established regulator of erythroblast survival Bcl-x L . SetD8 catalyzed H4K20me1 at a critical Gata2 cis element and restricted occupancy by an enhancer of Gata2 transcription, Scl/TAL1, thereby repressing Gata2 transcription. Elevating GATA-2 levels in erythroid precursors yielded a maturation block comparable to that induced by SetD8 downregulation. As lowering GATA-2 expression in the context of SetD8 knockdown did not rescue erythroid maturation, we propose that SetD8 regulation of erythroid maturation involves multiple target genes. These results establish SetD8 as a determinant of erythroid cell maturation and provide a framework for understanding how a broadly expressed histone-modifying enzyme mediates cell-type-specific GATA factor function.T he capacity of stem and progenitor cells to generate multiple cell lineages is orchestrated by cell-type-specific transcription factors that instigate lineage-specific genetic networks. These factors function with a cadre of broadly expressed transcription factors and coregulators, including chromatin-remodeling and -modifying enzymes. Cell-type-specific factors endow broadly expressed factors with activities important for establishing and/or maintaining the specialized transcriptome. Despite this paradigm, the functions of many broadly expressed chromatin-remodeling and -modifying enzymes have not been investigated in cell typespecific contexts. Considering the feasibility of devising smallmolecule strategies to target enzymes, it is instructive to identify enzymatic components mediating important biological processes. We have been addressing this problem by asking how GATA factors with specialized expression patterns and functions utilize broadly expressed coregulators to mediate cellular transitions required for development of hematopoietic stem cells (HSCs), progenitors, and differentiated progeny, including the erythrocyte.The family of dual zinc finger GATA transcription factors (1) recognize DNA with a WGATAR consensus (2, 3). GATA-2 is expressed predominantly in hematopoietic stem/progenitor cells (HSPCs), mast c...

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“…We demonstrated that GATA-1 directly represses Gata2 transcription using a complementation assay in the GATA-1-null proerythroblast-like cell G1E (71). GATA-1-mediated Gata2 repression was associated with GATA-1 occupancy at five dispersed regions of the Gata2 locus (Ϫ77, Ϫ3.9, Ϫ2.8, Ϫ1.8, and ϩ9.5 kb relative to the 1S promoter transcription start site), broad histone deacetylation, and RNA polymerase II expulsion (72,73,82). GATA-2 associates with these identical sites when Gata2 is transcriptionally active.…”

Section: Integrating Gata Factor Mechanisms Via Gata Switchesmentioning

confidence: 99%

GATA Switches as Developmental Drivers

Bresnick

Lee

Fujiwara

et al. 2010

Journal of Biological Chemistry

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254

288

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Transcriptional networks orchestrate complex developmental processes. Such networks are commonly instigated by master regulators of development. Considerable progress has been made in elucidating GATA factor-dependent genetic networks that control blood cell development. GATA-2 is required for the genesis and/or function of hematopoietic stem cells, whereas GATA-1 drives the differentiation of hematopoietic progenitors into a subset of the blood cell lineages. GATA-1 directly represses Gata2 transcription, and this involves GATA-1-mediated displacement of GATA-2 from chromatin, a process termed a GATA switch. GATA switches occur at numerous loci with critical functions, indicating that they are widely utilized developmental control tools.

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Context-dependent GATA Factor Function

Cited by 55 publications

References 62 publications

Context-dependent Function of Regulatory Elements and a Switch in Chromatin Occupancy between GATA3 and GATA2 Regulate Gata2 Transcription during Trophoblast Differentiation

Context-dependent Function of Regulatory Elements and a Switch in Chromatin Occupancy between GATA3 and GATA2 Regulate Gata2 Transcription during Trophoblast Differentiation

Epigenetic Determinants of Erythropoiesis: Role of the Histone Methyltransferase SetD8 in Promoting Erythroid Cell Maturation and Survival

GATA Switches as Developmental Drivers

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