A Family of POU-Domain and Pit-1 Tissue-Specific Transcription Factors in Pituitary and Neuroendocrine Development

1990 ◽  
Vol 52 (1) ◽  
pp. 773-791 ◽  
Author(s):  
H A Ingraham ◽  
V R Albert ◽  
R Chen ◽  
E B Crenshaw ◽  
H P E Xi He ◽  
...  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Michael Hamm ◽  
Pierre Sohier ◽  
Valérie Petit ◽  
Jérémy H. Raymond ◽  
Véronique Delmas ◽  
...  

AbstractWhile the major drivers of melanoma initiation, including activation of NRAS/BRAF and loss of PTEN or CDKN2A, have been identified, the role of key transcription factors that impose altered transcriptional states in response to deregulated signaling is not well understood. The POU domain transcription factor BRN2 is a key regulator of melanoma invasion, yet its role in melanoma initiation remains unknown. Here, in a BrafV600EPtenF/+ context, we show that BRN2 haplo-insufficiency promotes melanoma initiation and metastasis. However, metastatic colonization is less efficient in the absence of Brn2. Mechanistically, BRN2 directly induces PTEN expression and in consequence represses PI3K signaling. Moreover, MITF, a BRN2 target, represses PTEN transcription. Collectively, our results suggest that on a PTEN heterozygous background somatic deletion of one BRN2 allele and temporal regulation of the other allele elicits melanoma initiation and progression.


1994 ◽  
Vol 14 (10) ◽  
pp. 6907-6914
Author(s):  
P J Morris ◽  
T Theil ◽  
C J Ring ◽  
K A Lillycrop ◽  
T Moroy ◽  
...  

The Brn-3a, Brn-3b, and Brn-3c POU family transcription factors are closely related to one another and are members of the group IV subfamily of POU factors. Here we show that despite this close relationship, the factors have different effects on the activity of a target promoter: Brn-3a and Brn-3c stimulate the promoter whereas Brn-3b represses it. Moreover, Brn-3b can antagonize the stimulatory effect of Brn-3a on promoter activity and can also inhibit promoter activation by the Oct-2.1 POU factor. The difference in the transactivation activities of Brn-3a and Brn-3b is dependent upon the C-terminal region containing the POU domain of the two proteins, since exchange of this domain between the two factors converts Brn-3a into a repressor and Brn-3b into an activator.


2020 ◽  
Author(s):  
Yu Ge ◽  
Xiangshu Dong ◽  
Yuanzheng Liu ◽  
Ying Yang ◽  
Rulin Zhan

Abstract Background: The avocado (Persea americana) mesocarp and seed contain high-value oil with broad industrial applications. The oil contents in these two tissues vary considerably at maturity. Additionally, the molecular mechanism underlying the tissue-specific oil accumulation in the developing avocado mesocarp and seed remains unclear, which has hampered the exploration of the utility of avocado for oil production.Results: To clarify the mechanisms mediating the differences in oil contents and fatty acid compositions, the transcriptomes and oil bodies were compared between the oil-storing tissues during the fruit developmental period. The results revealed the increasing and fluctuating trends in the oil accumulation in the developing avocado mesocarp and seed, respectively. Additionally, striking differences in the lipid droplets between the mature mesocarp and seed were revealed in confocal microscopy images. Subsequently, the gene transcription profiles of the developing mesocarp and seed were characterized via a comprehensive transcriptome analysis involving second-generation sequencing and single-molecule real-time sequencing techniques. The tissue-specific transcription of lipid-related genes contributing to fatty acid synthesis, triacylglycerol assembly, and triacylglycerol storage was examined, with most of the lipid-related genes expressed at higher levels in the developing mesocarp than in the developing seed. A weighted gene co-expression network analysis uncovered 291 transcription factors that were commonly or uniquely correlated with the oil contents in the avocado mesocarp and seed. Moreover, 11 trans-acting and 79 cis-acting long non-coding RNAs were identified as common or unique to the developing avocado mesocarp and seed. These long non-coding RNAs may regulate the expression of 43 lipid-related genes. Finally, a network of genes associated with oil accumulation in the developing avocado mesocarp and seed was established.Conclusions: The results of this study further elucidate the tissue-specific oil biosynthesis and related regulatory network in the avocado mesocarp and seed. Furthermore, tissue-specific lipid-related genes, putative transcription factors, and putativelong non-coding RNAs affecting oil accumulation were identified. Our data may also be useful for characterizing tissue-specific oil accumulation at the transcriptomic level, thereby identifying candidate genes for improving the oil production of related plant species.


2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Andrew E. Teschendorff ◽  
Ning Wang

Abstract Tissue-specific transcription factors are frequently inactivated in cancer. To fully dissect the heterogeneity of such tumor suppressor events requires single-cell resolution, yet this is challenging because of the high dropout rate. Here we propose a simple yet effective computational strategy called SCIRA to infer regulatory activity of tissue-specific transcription factors at single-cell resolution and use this tool to identify tumor suppressor events in single-cell RNA-Seq cancer studies. We demonstrate that tissue-specific transcription factors are preferentially inactivated in the corresponding cancer cells, suggesting that these are driver events. For many known or suspected tumor suppressors, SCIRA predicts inactivation in single cancer cells where differential expression does not, indicating that SCIRA improves the sensitivity to detect changes in regulatory activity. We identify NKX2-1 and TBX4 inactivation as early tumor suppressor events in normal non-ciliated lung epithelial cells from smokers. In summary, SCIRA can help chart the heterogeneity of tumor suppressor events at single-cell resolution.


2019 ◽  
Vol 12 (1) ◽  
pp. 170081 ◽  
Author(s):  
Weiying Chen ◽  
Zhenyong Chen ◽  
Fuyan Luo ◽  
Mingli Liao ◽  
Shuhong Wei ◽  
...  

2007 ◽  
Vol 27 (21) ◽  
pp. 7425-7438 ◽  
Author(s):  
Maarten Hoogenkamp ◽  
Hanna Krysinska ◽  
Richard Ingram ◽  
Gang Huang ◽  
Rachael Barlow ◽  
...  

ABSTRACT The Ets family transcription factor PU.1 is crucial for the regulation of hematopoietic development. Pu.1 is activated in hematopoietic stem cells and is expressed in mast cells, B cells, granulocytes, and macrophages but is switched off in T cells. Many of the transcription factors regulating Pu.1 have been identified, but little is known about how they organize Pu.1 chromatin in development. We analyzed the Pu.1 promoter and the upstream regulatory element (URE) using in vivo footprinting and chromatin immunoprecipitation assays. In B cells, Pu.1 was bound by a set of transcription factors different from that in myeloid cells and adopted alternative chromatin architectures. In T cells, Pu.1 chromatin at the URE was open and the same transcription factor binding sites were occupied as in B cells. The transcription factor RUNX1 was bound to the URE in precursor cells, but binding was down-regulated in maturing cells. In PU.1 knockout precursor cells, the Ets factor Fli-1 compensated for the lack of PU.1, and both proteins could occupy a subset of Pu.1 cis elements in PU.1-expressing cells. In addition, we identified novel URE-derived noncoding transcripts subject to tissue-specific regulation. Our results provide important insights into how overlapping, but different, sets of transcription factors program tissue-specific chromatin structures in the hematopoietic system.


1993 ◽  
Vol 13 (4) ◽  
pp. 2564-2577 ◽  
Author(s):  
J C McDermott ◽  
M C Cardoso ◽  
Y T Yu ◽  
V Andres ◽  
D Leifer ◽  
...  

The myocyte enhancer-binding factor 2 (MEF2) site is an essential element of many muscle-specific enhancers and promoters that binds nuclear proteins from muscle and brain. Recently, we have cloned a family of MEF2 transcription factors produced by two genes that, at the mRNA level, are broadly expressed and produce tissue-specific isoforms by posttranscriptional processes (Y.-T. Yu, R. E. Breitbart, L. B. Smoot, Y. Lee, V. Mahdavi, and B. Nadal-Ginard, Genes Dev. 6:1783-1798, 1992). Here, we report the isolation and functional characterization of cDNA clones encoding four MEF2 factors derived from a separate gene that we have named hMEF2C. In contrast to those of the previously reported genes, the transcripts of the hMEF2C gene are restricted to skeletal muscle and brain. One of the alternate exons is exclusively present in brain transcripts. The products of this gene have DNA-binding and trans-activating activities indistinguishable from those of the previously reported MEF2 factors. The hMEF2C gene is induced late during myogenic differentiation, and its expression is limited to a subset of cortical neurons. The potential targets for this transcription factor in a subset of neurons are not known at this time. The strict tissue-specific pattern of expression of hMEF2C in comparison with the more ubiquitous expression of other MEF2 genes suggests a different mode of regulation and a potentially important role of hMEF2C factors in myogenesis and neurogenesis.


2007 ◽  
Vol 32 (1) ◽  
pp. 95-104 ◽  
Author(s):  
Shelley X. L. Zhang ◽  
Tina R. Searcy ◽  
Yiman Wu ◽  
David Gozal ◽  
Yang Wang

Expression patterns of monocarboxylate transporter 2 (MCT2) display mRNA diversity in a tissue-specific fashion. We cloned and characterized multiple mct2 5′-cDNA ends from the mouse and determined the structural organization of the mct2 gene. We found that transcription of this gene was initiated from five independent genomic regions that spanned >80 kb on chromosome 10, resulting in five unique exon 1 variants (exons 1a, 1b, 1c, 1d, and 1e) that were then spliced to the common exon 2. Alternative splicing of four internal exons (exons AS1, AS2, AS3, and exon 3) greatly increased the complexity of mRNA diversity. While exon 1c was relatively commonly used for transcription initiation in various tissues, other exon 1 variants were used in a tissue-specific fashion, especially exons 1b and 1d that were used exclusively for testis-specific expression. Sequence analysis of 5′-flanking regions upstream of exons 1a, 1b, and 1c revealed the presence of numerous potential binding sites for ubiquitous transcription factors in all three regions and for transcription factors implicated in testis-specific or hypoxia-induced gene expression in the 1b region. Transient transfection assays demonstrated that each of the three regions contained a functional promoter and that the in vitro, cell type-specific activities of these promoters were consistent with the tissue-specific expression pattern of the mct2 gene in vivo. These results indicate that tissue-specific expression of the mct2 gene is controlled by multiple alternative promoters and that both alternative promoter usage and alternative splicing contribute to the remarkable mRNA diversity of the gene.


Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1373 ◽  
Author(s):  
Herring ◽  
Elison ◽  
Tessem

The Nr4a family of nuclear hormone receptors is composed of three members—Nr4a1/Nur77, Nr4a2/Nurr1 and Nr4a3/Nor1. While currently defined as ligandless, these transcription factors have been shown to regulate varied processes across a host of tissues. Of particular interest, the Nr4a family impinge, in a tissue dependent fashion, on cellular proliferation, apoptosis and fuel utilization. The regulation of these processes occurs through both nuclear and non-genomic pathways. The purpose of this review is to provide a balanced perspective of the tissue specific and Nr4a family member specific, effects on cellular proliferation, apoptosis and fuel utilization.


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