Gata4 expression in lateral mesoderm is downstream of BMP4 and is activated directly by Forkhead and GATA transcription factors through a distal enhancer element

The GRU (glucocorticoid-response unit) within the distal enhancer of the gene encoding carbamoyl-phosphate synthase, which comprises REs (response elements) for the GR (glucocorticoid receptor) and the liver-enriched transcription factors FoxA (forkhead box A) and C/EBP (CCAAT/enhancer-binding protein), and a binding site for an unknown protein denoted P3, is one of the simplest GRUs described. In this study, we have established that the activity of this GRU depends strongly on the positioning and spacing of its REs. Mutation of the P3 site within the 25 bp FoxA–GR spacer eliminated GRU activity, but the requirement for P3 could be overcome by decreasing the length of this spacer to ≤12 bp, by optimizing the sequence of the REs in the GRU, and by replacing the P3 sequence with a C/EBPβ sequence. With spacers of ≤12 bp, the activity of the GRU depended on the helical orientation of the FoxA and GR REs, with highest activities observed at 2 and 12 bp respectively. Elimination of the 6 bp C/EBP–FoxA spacer also increased GRU activity 2-fold. Together, these results indicate that the spatial positioning of the transcription factors that bind to the GRU determines its activity and that the P3 complex, which binds to the DNA via a 75 kDa protein, functions to facilitate interaction between the FoxA and glucocorticoid response elements when the distance between these transcription factors means that they have difficulties contacting each other.

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Somatostatin gene upstream enhancer element activated by a protein complex consisting of CREB, Isl-1-like, and alpha-CBF-like transcription factors.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)42357-5 ◽

1992 ◽

Vol 267 (18) ◽

pp. 12876-12884 ◽

Cited By ~ 1

Author(s):

M Vallejo ◽

L Penchuk ◽

J.F. Habener

Keyword(s):

Transcription Factors ◽

Protein Complex ◽

Enhancer Element

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Multi-omic profiling of pituitary thyrotropic cells and progenitors

BMC Biology ◽

10.1186/s12915-021-01009-0 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Alexandre Z. Daly ◽

Lindsey A. Dudley ◽

Michael T. Peel ◽

Stephen A. Liebhaber ◽

Stephen C. J. Parker ◽

...

Keyword(s):

Transcription Factors ◽

Pituitary Gland ◽

Cell Lines ◽

Binding Sites ◽

Critical Factor ◽

Regulatory Elements ◽

Thyroid Stimulating Hormone ◽

Neuroendocrine Cells ◽

Bzip Transcription Factor ◽

Enhancer Element

Abstract Background The pituitary gland is a neuroendocrine organ containing diverse cell types specialized in secreting hormones that regulate physiology. Pituitary thyrotropes produce thyroid-stimulating hormone (TSH), a critical factor for growth and maintenance of metabolism. The transcription factors POU1F1 and GATA2 have been implicated in thyrotrope fate, but the transcriptomic and epigenomic landscapes of these neuroendocrine cells have not been characterized. The goal of this work was to discover transcriptional regulatory elements that drive thyrotrope fate. Results We identified the transcription factors and epigenomic changes in chromatin that are associated with differentiation of POU1F1-expressing progenitors into thyrotropes using cell lines that represent an undifferentiated Pou1f1 lineage progenitor (GHF-T1) and a committed thyrotrope line that produces TSH (TαT1). We compared RNA-seq, ATAC-seq, histone modification (H3K27Ac, H3K4Me1, and H3K27Me3), and POU1F1 binding in these cell lines. POU1F1 binding sites are commonly associated with bZIP transcription factor consensus binding sites in GHF-T1 cells and Helix-Turn-Helix (HTH) or basic Helix-Loop-Helix (bHLH) factors in TαT1 cells, suggesting that these classes of transcription factors may recruit or cooperate with POU1F1 binding at unique sites. We validated enhancer function of novel elements we mapped near Cga, Pitx1, Gata2, and Tshb by transfection in TαT1 cells. Finally, we confirmed that an enhancer element near Tshb can drive expression in thyrotropes of transgenic mice, and we demonstrate that GATA2 enhances Tshb expression through this element. Conclusion These results extend the ENCODE multi-omic profiling approach to the pituitary gland, which should be valuable for understanding pituitary development and disease pathogenesis. Graphical abstract

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The vacuolar amino acid transport system is a novel, direct target of GATA transcription factors

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbaa041 ◽

2021 ◽

Vol 85 (3) ◽

pp. 587-599

Author(s):

Akane Sato ◽

Takumi Kimura ◽

Kana Hondo ◽

Miyuki Kawano-Kawada ◽

Takayuki Sekito

Keyword(s):

Transcription Factors ◽

Amino Acid ◽

Amino Acid Transport ◽

Amino Acid Transporters ◽

Acid Transport ◽

Amino Acid Transport System ◽

Gata Transcription Factor ◽

Gata Transcription Factors ◽

Acid Status ◽

Direct Target

ABSTRACT In Saccharomyces cerevisiae, Avt4 exports neutral and basic amino acids from vacuoles. Previous studies have suggested that the GATA transcription factors, Gln3 and Gat1, which are key regulators that adapt cells in response to changes in amino acid status, are involved in the AVT4 transcription. Here, we show that mutations in the putative GATA-binding sites of the AVT4 promoter reduced AVT4 expression. Consistently, a chromatin immunoprecipitation (ChIP) assay revealed that Gat1-Myc13 binds to the AVT4 promoter. Previous microarray results were confirmed that gln3∆gat1∆ cells showed a decrease in expression of AVT1 and AVT7, which also encode vacuolar amino acid transporters. Additionally, ChIP analysis revealed that the AVT6 encoding vacuolar acidic amino acid exporter represents a new direct target of the GATA transcription factor. The broad effect of the GATA transcription factors on the expression of AVT transporters suggests that vacuolar amino acid transport is integrated into cellular amino acid homeostasis.

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