Search results for GATA6

Showing 16 results out of 33

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Protein (1 results from a total of 1)

Identifier: R-HSA-452902
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: GATA6: Q92908

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-2888975
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: GATA6: ENSEMBL:ENSG00000141448

Reaction (5 results from a total of 19)

Identifier: R-HSA-9734573
Species: Homo sapiens
Compartment: nucleoplasm
The GATA6 gene is transcribed to yield mRNA and the mRNA is translated to yield GATA6 protein. GATA6 is expressed in the cardiac crescent of cardiac progenitor cells and transcription is directly activated by NKX2-5 (inferred from mouse homologs).
Identifier: R-HSA-9823977
Species: Homo sapiens
Compartment: nucleoplasm
In mouse embryos, Gata6 is expressed in the primitive streak and continues expression in the definitive endoderm (Morrisey et al. 1996, Freyer et al. 2015, Wen et al. 2017). In human embryonic stem cell models, GATA6 is required for formation of definitive endoderm and pancreas development (Tiyaboonchai et al.2017, Chia et al. 2019). In the definitive endoderm, NODAL signaling activates transcription of GATA6 via the phosphorylation of SMAD2 and SMAD3, which bind the GATA6 promoter (inferred from human pluripotent stem cells in McLean et al. 2007, Vallier et al. 2009, Brown et al. 2011, Yang et al. 2020). The antisense transcript GATA6-AS1 lncRNA from an upstream region of the GATA6 coding sequence enhances the interaction of SMAD2,3 with the GATA6 promoter (Yang et al. 2020). GATA6-AS1 is required for differentiation of definitive endoderm from embryonic stem cells (Yang et al. 2020)
Identifier: R-HSA-9734590
Species: Homo sapiens
Compartment: nucleoplasm
NKX2-5 binds the promoter of the GATA6 gene (inferred from mouse homologs).
Identifier: R-HSA-5685296
Species: Homo sapiens
Compartment: nucleoplasm
Transcription factor GATA-6 (GATA6) binds to a cis-acting element in the surfactant protein A1-3 (SFTPAs) gene promoters, activating the transcription of the genes (Bruno et al. 2000).
Identifier: R-HSA-9823959
Species: Homo sapiens
Compartment: nucleoplasm
NODAL signaling in the anterior primitive streak causes phosphorylation of SMAD2 and SMAD3 which co-translocate with SMAD4 to the nucleus and together bind the promoter of the GATA6 gene (inferred from human pluripotent stem cells in Brown et al. 2011, Yang et al. 2020). The antisense transcript GATA6-AS1 from an upstream region of the GATA6 coding region enhances the interaction between SMAD2,3 and the GATA6 promoter (Yang et al. 2020). GATA6-AS1 is required for differentiation of definitive endoderm from embryonic stem cells (Yang et al. 2020).

Complex (5 results from a total of 8)

Identifier: R-HSA-5685293
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5683868
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-9734591
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-9823969
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-9735252
Species: Homo sapiens
Compartment: nucleoplasm

RNA Sequence (1 results from a total of 1)

Identifier: R-HSA-9827615
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSEMBL:ENST00000579431

Pathway (3 results from a total of 3)

Identifier: R-HSA-9823730
Species: Homo sapiens
The endoderm in mammalian embryos originates from two different populations of cells: the visceral endoderm, which is present before gastrulation as the hypoblast underlying the epiblast, and the definitive endoderm, which is derived from epiblast cells ingressing through the anterior-most region of the primitive streak. After ingression, the cells of the definitive endoderm then intercalate with the cells of the visceral endoderm to form the embryonic endoderm that will give rise to the gut and visceral organs associated with the gut such as the pancreas and liver (reviewed in Lewis and Tam 2006, Nowotschin et al. 2019). In the discoid human gastrula (differs from the rodent gastrula which acquires a cup shape), the endoderm initially is organized in a flat epithelial sheet that later rolls into a tube to form the gut. Due to ethical considerations, research on gastrulation is undertaken primarily in non-human primate species (for example Bergmann et al. 2022) and stem cells (D'Amour et al. 2005, reviewed in Salehin et al. 2022), which have provided insight into germ layer formation in human embryos.
The definitive endoderm originates in the anterior region of the primitive streak where there are high levels of NODAL signaling (inferred from mouse embryos in Vincent et al. 2003) and lower levels of BMP signaling (inferred from mouse embryos in Bachiller et al. 2000) and Wnt signaling (inferred from mouse embryos in Mukhopadhyay et al. 2001). In mouse, Eomesodermin (EOMES), whose expression is activated by NODAL signaling via SMAD2 and SMAD3 in the primitive streak, is required for formation of both mesoderm and endoderm (Arnold et al. 2008). Experiments in human embryonic stem cells and mouse embryos indicate that EOMES is a core element of a gene regulatory network that specifies definitive endoderm by activating expression of transcription factors such as FOXA2 and SOX17 which then activate sets of endodermally expressed genes (Teo et al. 2011, Chia et al. 2019). As endoderm progenitors enter the primitive streak they redistribute E-cadherin (CDH1) on their surface, which may play a role in sorting the cells into an epithelial layer (inferred from mouse homologs in Viotti et al. 2014). Unlike mesoderm, endoderm progenitors do not undergo a complete epithelial to mesenchymal transition (EMT) (inferred from mouse embryos and stem cells in Scheibner et al. 2021). They do not switch cadherin expression from E-cadherin (CDH1) to N-cadherin (CDH2) and do not require the EMT transcription factor SNAI1 (in ferred from mouse homologs in Scheibner et al. 2021). The endodermal transcription factor FOXA2 may repress EMT activity (in ferred from the mouse homolog in Scheibner et al. 2021).
Though no single marker gene is expressed exclusively in definitive endoderm, the definitive endoderm is characterized by the expression of a combination of genes, including FOXA2, SOX17, GATA4, GATA6, CXCR4, GSC, and E-cadherin (CDH1). CDH1, a general marker of epithelial cells, and the chemokine receptor CXCR4 are often used together as surface markers of definitive endoderm (inferred from mouse homologs in Yasunaga et al. 2005).
Identifier: R-HSA-9844594
Species: Homo sapiens
EBF2 (Early B-cell factor 2) is a transcription factor that marks committed brown and beige preadipocytes. EBF2 cooperates with PPARG, a master regulator of adipogenesis, to activate the brown/beige adipocyte thermogenic program (inferred from mouse homologs in Rajakumari et al. 2013). In white adipocytes, the activity of EBF2 is negatively regulated by binding of the transcription factor ZNF423, a key transcription factor for white adipocyte differentiation. In brown/beige fate-committed cells, the interaction between ZNF423 and EBF2 is impeded by BMP7, which acts as a positive regulator of brown/beige adipogenesis (inferred from mouse homologs in Shao et al. 2016; Shao et al. 2021). Direct transcriptional targets of EBF2 include PRDM16, UCP1, and PPARA genes. Other marker genes of brown/beige adipocytes, such as CIDEA, PPARGC1A, COX7A, and DIO2 are positively regulated by EBF2 and probably also direct targets of EBF2 (inferred from mouse homologs in Rajakumari et al. 2013; Wang et al. 2014; Stine et al. 2016; Shapira et al. 2017; Lai et al. 2017; Angueira et al. 2020). Based on mouse studies, EBF1 may function partially redundantly with EBF2 in regulation of thermogenesis genes (Angueira et al. 2020). Transcriptional activity of EBF2 is positively regulated by binding of the long noncoding RNA (lncRNA) Blnc1 (inferred from mouse homologs in Zhao et al. 2014; Mi et al. 2017). Based on mouse studies, EBF2 was reported to recruit the BAF chromatin remodeling complex to activate the transcription of target genes (Shapira et al. 2017; Liu et al. 2020). In addition to PPARG, based on mouse studies, EBF2 was reported to cooperate with other transcription factors such as SIX1 during brown/beige adipogenesis (Brunmeir et al. 2016). Besides ZNF423, based on mouse studies, other transcription factors, such as ID1 (Patil et al. 2017) and TLE3 (Pearson et al. 2019), have been reported to act as inhibitors of EBF2-mediated transcription. The transcription factor GATA6 was reported to directly stimulate EBF2 transcription during mouse beige/brown thermogenesis (Jun et al. 2023). Besides BPM7, BPM9-mediated upregulation of FGFR3 (Yamamoto et al. 2022), and FGF11 (Jiang et al. 2023) have been reported as indirect activators of EBF2 transcriptional activity in mouse and goat, respectively. ZAG (Zinc-alpha2-glycoprotein), a tumor secretory factor, has been reported to stimulate EBF2 expression, which contributes to white adipose tissue browning and energy wasting in cancer-related cachexia (Elattar et al. 2018). In the single cell atlas of human white adipose tissue (Emont et al. 2022) it was reported that the EBF2-positive hAd6 white adipocyte subpopulation with UCP1 expression, consistent with the beige profile, shows an association with increased BMI and visceral adiposity. For review, please refer to Wang and Seale 2016.
Identifier: R-HSA-9733709
Species: Homo sapiens
Gradients of Bone Morphogenetic Protein (BMP), Wingless-related integration site (WNT), and NODAL promote the formation of cardiac progenitors anteriolateral to the primitive streak during gastrulation (reviewed in Munoz-Chapuli and Perez-Pomares 2010, Cui et al. 2018, Prummel et al. 2020, Witman et al. 2019, Miyamoto e al. 2021). Eomesodermin (EOMES) and TBXT (T, Brachyury) expressed in the cardiac mesoderm activate expression of MESP1, a master regulator of cardiogenesis and the first observed marker of cardiac progenitors. MESP1-expressing cells migrate anteriorly towards the midline to form the cardiac crescent posterior to the head folds at about 2 weeks of gestation in humans (E7.5 in mice).

Within the cardiac crescent, two populations of cells can be identified based on gene expression and timing of contribution to the developing heart: the first heart field (FHF) forms the initial heart tube and contributes to the systemic ventricle (the left ventricle in crocodilians, birds, and mammals), the septum, and, to a lesser extent, the atria; the second heart field (SHF) extends the poles of the heart and contributes to the atria, the outflow tract, the septum, and the right ventricle, which is responsible for pulmonary circulation and distinguishes crocodilians, birds, and mammals (reviewed in Meilhac and Buckingham 2018).

At about 3 weeks gestation in humans (E8 in mice), FHF cells migrate axially to the midline and fuse to form the heart tube. Elongation of the heart tube leads to rightward looping and eventual formation of atria and ventricles (reviewed in Desgrange et al. 2018). FHF cells do not proliferate as much as SHF cells and mostly differentiate into cardiomyocytes due to the actions of myocardial differentiation factors such as NKX2-5, GATA4, TBX5, and HAND1. SHF cells are initially located in the posterior region of the cardiac crescent then, during formation of the heart tube, become located at the arterial and venous poles of the heart tube. SHF cells proliferate more than FHF cells and can differentiate to form cardiomyocytes, endothelial cells, smooth muscle cells, and fibroblasts. A reservoir of SHF progenitors located at the core of the pharyngeal mesoderm continuously contributes to the developing heart. Proliferating SHF cells express FGF8 and FGF10 driven by ISL1 and TBX1.

Cardiac progenitors are regulated by a distinct set of transcription factors and mutations in these factors and other factors involved in gene expression are responsible for congenital heart defects (reviewed in Diab et al. 2021, Houyel and Meilhac 2021, Kodo et al. 2021, Miyamoto et al. 2021, Lescroart and Zaffran 2022, Wang et al. 2022). Additionally, combinations of these transcription factors are now being used to reprogram fibroblasts and other cell types into cardiomyocytes for repairing damaged hearts (reviewed in Adams et al. 2021, Garry et al. 2021, Kim et al. 2022, Thomas et al. 2022, Zhu et al. 2022). TBXT (T, Brachyury) is expressed early in developing mesoderm and is activated by WNT signaling, which maintains proliferation and is subsequently downregulated during differentiation. Activation of MESP1 expression by TBXT and EOMES occurs early in gastrulation. MESP1 is expressed in both the FHF and the SHF. MESP1, in turn, directly activates two key regulators of cardiac development: GATA4 and NKX2-5 (NKX2.5, the ortholog of Tinman in Drosophila). Bone Morphogenetic Protein (BMP) signaling originating from BMPs secreted by underlying endoderm also enhances expression of GATA4 and NKX2-5, apparently through binding of SMAD proteins to the promoters of GATA4 and NKX2-5. GATA4 and NKX2-5 proteins, in turn, regulate each other's expression and directly interact to regulate downstream target genes. NKX2-5 directly activates GATA6 throughout the cardiac mesoderm.

The FHF is characterized by expression of TBX5 and HCN4; the SHF is characterized by transient expression of TBX1, ISL1, FGF8, FGF10, and SIX2. In the FHF, NKX2-5 binds the promoter of the TBX5 gene and activates transcription. TBX5, in turn, directly activates expression of SRF. TBX5 protein interacts directly with NKX2-5 and GATA4 proteins to activate further downstream targets. Sonic hedgehog (SHH) from the pharyngeal endoderm and WNT signaling maintain proliferation of SHF cells, In the SHF, TBX1, GATA4 and LEF1:CTNN1 (LEF1:Beta-catenin from Wnt signaling) directly activate ISL1, characteristic of SHF cells, and ISL1 then activates expression of HAND2 (dHAND), also characteristic of SHF cells.
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