Combinatorial regulation of tissue specification by GATA and FOG factors

Chlon, Timothy M.; Crispino, John D.

doi:10.1242/dev.080440

Cited by 84 publications

(81 citation statements)

References 136 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The complexity of GATA3 as a regulator of tumor cell biology depends partly on its transcriptional cofactors. GATA3 associates with FOG1 or FOG2, which can function as coactivators or corepressors of target genes (46). FOG2 is critical for normal cardiac development in mice, and germline FOG2 mutations are associated with congenital cardiac defects in humans (47,48).…”

Section: Discussionmentioning

confidence: 99%

“…FOG2-deficient epicardial cells can undergo EMT (48), as we observed in KP cells, but GATA3 deficiency shifts KP cells into an epithelial state that is refractory to TGF-β treatment (37), suggesting that FOG2 mediates its actions in part through GATA factors other than GATA3. Unlike FOG1, which binds preferentially to GATA1, GATA2, and GATA3 and is expressed predominantly in hematopoietic cells, FOG2 binds to GATA3, GATA4, GATA5, and GATA6 and is expressed broadly in epithelial, myocardial, neuronal, and hepatic cells (46). GATA factors share varying degrees of homologic features and have functions that are partially interchangeable.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

ZEB1 sensitizes lung adenocarcinoma to metastasis suppression by PI3K antagonism

et al. 2014

View full text Add to dashboard Cite

IntroductionLung cancer is the foremost cause of cancer-related mortality, with high incidence rates, robust metastatic propensity, and frequent de novo and acquired resistance to therapy (1). Even in the setting of "addiction" to mutant receptor tyrosine kinases (RTKs) that are pharmacologically targetable, tumors undergo only transient responses to targeted therapy and subsequently develop drug resistance that frequently results in death (2). The incidence of KRAS mutations exceeds that of RTK mutations in lung adenocarcinoma, and currently available therapeutic strategies do not effectively target mutant KRAS (3). KRAS-mutant lung adenocarcinomas commonly harbor oncogenic mutations in TP53 and STK11 that confer metastatic capacity (4). Thus, inhibition of mutant oncoproteins reduces tumor burden but does not eradicate disease in patients with lung cancer, warranting the development of other treatment strategies that complement the beneficial effects of tumor cytoreduction.In the "migrating stem cell hypothesis," metastases arise from a small population of tumor cells with the capacity to undergo epithelial-mesenchymal transition (EMT), a reversible process characterized by a loss of polarized features, detachment from neighboring cells, increased motility and invasion, and resistance to standard cytotoxic chemotherapy (5). EMT is induced by several

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

ZEB1 sensitizes lung adenocarcinoma to metastasis suppression by PI3K antagonism

et al. 2014

View full text Add to dashboard Cite

show abstract

“…GATA factors are either transcriptional activators or repressors (reviewed by Chlon and Crispino, 2012). GATA factor transcriptional repressor activity requires interaction with either of the transcriptional co-factors FOG1 (ZFPM1) or FOG2 (which in turn recruit the co-repressors NuRD and CtBP).…”

Section: Gata4 Can Interact With Gli Factorsmentioning

confidence: 99%

BMP-mediated induction of GATA4/5/6 blocks somitic responsiveness to SHH

et al. 2014

View full text Add to dashboard Cite

The relative timing of SHH and BMP signals controls whether presomitic mesoderm (PSM) cells will adopt either a chondrogenic or lateral plate mesoderm fate. Here we document that SHH-mediated induction of Nkx3.2 maintains the competence of somitic cells to initiate chondrogenesis in response to subsequent BMP signals by repressing BMP-dependent induction of GATA genes. Conversely, administration of BMP signals to PSM or forced expression of GATA family members in chick PSM explants blocks induction of hedgehogdependent gene expression. We demonstrate that GATA factors can interact with Gli factors and can recruit the transcriptional co-factor FOG1 (ZFPM1) to the regulatory region of the mouse Gli1 gene, repressing the induction of Gli1 by SHH by binding to both GATA and Gli binding sites. Knockdown of FOG1 reverses the ability of GATA factors to repress Gli1 expression. Our findings uncover a novel role for GATA transcription factors as repressors of hedgehog signaling, and document that NKX3.2 maintains the ability of sclerotomal cells to express SHH transcriptional targets in the presence of BMP signals by repressing the induction of Gata4/5/6.

show abstract

“…[1][2][3][4][5] It accomplishes this by both activating lineage specifying genes and repressing progenitor maintenance genes through a variety of gene regulatory mechanisms that depend on context-dependent co-factor interactions. 6 Importantly, GATA1 interacts with and controls the expression of many other lineage-specifying transcription factors to co-ordinately repress factors promoting other cell fates while activating those of megakaryocytes and erythrocytes. 7,8 The lineage fate decision of the MEP towards either the erythroid or megakaryocyte fate is controlled by complex interactions among transcription factors.…”

Section: Introductionmentioning

confidence: 99%

Global transcriptome and chromatin occupancy analysis reveal the short isoform of GATA1 is deficient for erythroid specification and gene expression

et al. 2015

View full text Add to dashboard Cite

GATA1 is a master transcriptional regulator of the differentiation of several related myeloid blood cell types, including erythrocytes and megakaryocytes. Germ-line mutations that cause loss of full length GATA1, but allow for expression of the short isoform (GATA1s), are associated with defective erythropoiesis in a subset of patients with Diamond Blackfan Anemia. Despite extensive studies of GATA1s in megakaryopoiesis, the mechanism by which GATA1s fails to support normal erythropoiesis is not understood. In this study, we used global gene expression and chromatin occupancy analysis to compare the transcriptional activity of GATA1s to GATA1. We discovered that compared to GATA1, GATA1s is less able to activate the erythroid gene expression program and terminal differentiation in cells with dual erythroid-megakaryocytic differentiation potential. Moreover, we found that GATA1s bound to many of its erythroid-specific target genes less efficiently than full length GATA1. These results suggest that the impaired ability of GATA1s to promote erythropoiesis in DBA may be caused by failure to occupy erythroid-specific gene regulatory elements. Global transcriptome and chromatin occupancy analysis reveal the short isoform of GATA1 is deficient for erythroid specification and gene expression ABSTRACT MethodsCell culture G1ME cells were maintained in 1% THPO-conditioned media or in media containing THPO, SCF and EPO, as described. 3 Retroviral transduction and constructsRetroviral supernatant was prepared and applied to cells, as previously described.32 MigR1 constructs containing HA-tagged GATA1 and GATA1s have been described previously.

show abstract

Combinatorial regulation of tissue specification by GATA and FOG factors

Cited by 84 publications

References 136 publications

ZEB1 sensitizes lung adenocarcinoma to metastasis suppression by PI3K antagonism

ZEB1 sensitizes lung adenocarcinoma to metastasis suppression by PI3K antagonism

BMP-mediated induction of GATA4/5/6 blocks somitic responsiveness to SHH

Global transcriptome and chromatin occupancy analysis reveal the short isoform of GATA1 is deficient for erythroid specification and gene expression

Contact Info

Product

Resources

About