FOG-1-mediated recruitment of NuRD is required for cell lineage re-enforcement during haematopoiesis

Gao, Zhiguang; Huang, Zan; Olivey, Harold E.; Gurbuxani, Sandeep; Crispino, John D.; Svensson, E. C.

doi:10.1038/emboj.2009.368

Cited by 54 publications

(53 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The NuRD complex associates with FOG-1 (16) and is an important determinant of GATA-1-mediated regulation of transcription and hematopoiesis (17,18). We predicted that FOG-1-regulated, SetD8/GATA-1-corepressed genes would also require Mi2β, a key ATPase subunit of the NuRD complex (47,48).…”

Section: Resultsmentioning

confidence: 99%

“…The GATA-1-interacting coregulator Friend of GATA-1 (FOG-1) mediates GATA-1-dependent activation and repression in a context-dependent manner (12,13). FOG-1 facilitates GATA-1 chromatin occupancy (14,15) and interacts with the nucleosome remodeling and deacetylase (NuRD) chromatin remodeling complex (16) containing the ATPase CHD4 (Mi2β), which is required for development of erythroid and other hematopoietic lineages (17,18). GATA-1 also recruits the chromatin remodeler BRG1 (19,20), the histone acetyltransferase CBP/p300 (21), and the mediator complex component Med1 (22,23).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Establishing a hematopoietic genetic network through locus-specific integration of chromatin regulators

DeVilbiss

Boyer

Bresnick

2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The establishment and maintenance of cell type-specific transcriptional programs require an ensemble of broadly expressed chromatin remodeling and modifying enzymes. Many questions remain unanswered regarding the contributions of these enzymes to specialized genetic networks that control critical processes, such as lineage commitment and cellular differentiation. We have been addressing this problem in the context of erythrocyte development driven by the transcription factor GATA-1 and its coregulator Friend of GATA-1 (FOG-1). As certain GATA-1 target genes have little to no FOG-1 requirement for expression, presumably additional coregulators can mediate GATA-1 function. Using a genetic complementation assay and RNA interference in GATA-1-null cells, we demonstrate a vital link between GATA-1 and the histone H4 lysine 20 methyltransferase PR-Set7/SetD8 (SetD8). GATA-1 selectively induced H4 monomethylated lysine 20 at repressed, but not activated, loci, and endogenous SetD8 mediated GATA-1-dependent repression of a cohort of its target genes. GATA-1 used different combinations of SetD8, FOG-1, and the FOG-1-interacting nucleosome remodeling and deacetylase complex component Mi2β to repress distinct target genes. Implicating SetD8 as a context-dependent GATA-1 corepressor expands the repertoire of coregulators mediating establishment/maintenance of the erythroid cell genetic network, and provides a biological framework for dissecting the cell type-specific functions of this important coregulator. We propose a coregulator matrix model in which distinct combinations of chromatin regulators are required at different GATA-1 target genes, and the unique attributes of the target loci mandate these combinations.

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Establishing a hematopoietic genetic network through locus-specific integration of chromatin regulators

DeVilbiss

Boyer

Bresnick

2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…A 12-amino acid sequence in the FOG-1 N terminus binds NuRD, and NuRD co-occupies chromatin sites with GATA-1 at GATA-1-activated and -repressed genes (15,17,39). Knock-in mice bearing mutations that disrupt the FOG-1-NuRD interaction are anemic and exhibit macrothrombocytopenia (17,39).…”

Section: Trans-acting Factor-driven Target Gene Relocalization Inmentioning

confidence: 99%

“…Knock-in mice bearing mutations that disrupt the FOG-1-NuRD interaction are anemic and exhibit macrothrombocytopenia (17,39). These mice were bred to transgenic mice containing a human ␤-globin locus transgene to assess whether the FOG-1-NuRD interaction mediates developmental repression of fetal globin genes (40).…”

Section: Trans-acting Factor-driven Target Gene Relocalization Inmentioning

confidence: 99%

“…Thus, molecular determinants for activation versus maintenance can differ in a locus-specific manner. Despite strong evidence implicating FOG-1 collaboration with the NuRD complex (15,17,39), and the dual FOG-1/Mi-2␤ requirement to activate Slc4a1, FOG-1 and Mi-2␤ are differentially important for maintaining Slc4a1 transcription. These results illustrate a novel mechanism by which a cell type-specific trans-acting factor differentially utilizes coregulators to mediate activation versus maintenance of members of its target gene ensemble.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Relocalizing Genetic Loci into Specific Subnuclear Neighborhoods

Lee¹,

Johnson²,

Boyer³

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

A poorly understood problem in genetics is how the threedimensional organization of the nucleus contributes to establishment and maintenance of transcriptional networks. Genetic loci can reside in chromosome "territories" and undergo dynamic changes in subnuclear positioning. Such changes appear to be important for regulating transcription, although many questions remain regarding how loci reversibly transit in and out of their territories and the functional significance of subnuclear transitions. We addressed this issue using GATA-1, a master regulator of hematopoiesis implicated in human leukemogenesis, which often functions with the coregulator Friend of GATA-1 (FOG-1). In a genetic complementation assay in GATA-1-null cells, GATA-1 expels FOG-1-dependent target genes from the nuclear periphery during erythroid maturation, but the underlying mechanisms are unknown. We demonstrate that GATA-1 induces extrusion of the ␤-globin locus away from its chromosome territory at the nuclear periphery, and extrusion precedes the maturation-associated transcriptional surge and morphological transition. FOG-1 and its interactor Mi-2␤, a chromatin remodeling factor commonly linked to repression, were required for locus extrusion. Erythroid Krüppel-like factor, a pivotal regulator of erythropoiesis that often co-occupies chromatin with GATA-1, also promoted locus extrusion. Disruption of transcriptional maintenance did not restore the locus subnuclear position that preceded activation. These results lead to a model for how a master developmental regulator relocalizes a locus into a new subnuclear neighborhood that is permissive for high level transcription as an early step in establishing a cell type-specific genetic network. Alterations in the regulatory milieu can abrogate maintenance without reversion of locus residency back to its original neighborhood.trans-Acting factors establish cell type-specific and developmental stage-specific transcriptional networks as a critical step in the development of multicellular organisms. Many questions remain unanswered regarding how genetic networks are established and maintained. An important parameter is the threedimensional organization of the cell nucleus, in which chromosomes occupy distinct territories, and regulatory factors reside in specific nuclear bodies that exert specialized functions (1-3).

show abstract

Transcriptional Regulation of Platelet Formation: Harnessing the Complexity for Efficient Platelet Production In Vitro

Tijssen

Moreau

Ghevaert

2016

Molecular and Cellular Biology of Platelet Formation

View full text Add to dashboard Cite

It is now common knowledge that specific repertoires of transcription factors (TFs) determine a cell's protein content and thereby its phenotype. The expression of a given TF is not necessarily cell specific, and many TFs play a pivotal role in several different cell types. For example, TAL1, FLI1, RUNX1, ERG and GATA2 are important regulators of stem cells, but also play a vital role in megakaryopoiesis. Although the megakaryocyte (MK) and its closest relative, the red blood cell, share key TFs like GATA1 and NFE2, the bifurcation between the two lineages has been associated with pairs of TFs that act as a toggle switch (such as FLI1 and KLF1). This chapter will summarise the current knowledge of key transcriptional regulators of MK differentiation and how some of these TFs, despite being expressed in several cell types, can impose MK cell identity. Since the discovery of TPO in 1994, our knowledge of MK biology and differentiation has increased exponentially, but we still lack a deep understanding of what triggers the transition from MK growth and maturation to proplatelet formation. We describe how some well-known TFs control the expression of proteins that play a pivotal role in the dramatic cytoplasmic and cytoskeletal events that accompany proplatelet formation. Finally, we show how TFs can be harnessed in a powerful way to produce MKs and, potentially, platelets in vitro for future clinical applications.

show abstract

FOG-1-mediated recruitment of NuRD is required for cell lineage re-enforcement during haematopoiesis

Cited by 54 publications

References 52 publications

Establishing a hematopoietic genetic network through locus-specific integration of chromatin regulators

Establishing a hematopoietic genetic network through locus-specific integration of chromatin regulators

Relocalizing Genetic Loci into Specific Subnuclear Neighborhoods

Transcriptional Regulation of Platelet Formation: Harnessing the Complexity for Efficient Platelet Production In Vitro

Contact Info

Product

Resources

About