Transcriptional activity of FIGLA, NEUROG2, and EGR1 transcription factors associated with polymorphisms in the proximal regulatory region of GPR54 gene in cattle

2020 ◽  
Vol 218 ◽  
pp. 106506 ◽  
Author(s):  
Jin Cheng ◽  
Wen-Juan Qin ◽  
Nyamsuren Balsai ◽  
Xuan-Jian Shang ◽  
Meng-Ting Zhang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activity ◽  
Regulatory Region ◽  
Factors Associated ◽  
Gpr54 Gene

scholarly journals The AML-associated K313 mutation enhances C/EBPα activity by leading to C/EBPα overexpression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ian Edward Gentle ◽  
Isabel Moelter ◽  
Mohamed Tarek Badr ◽  
Konstanze Döhner ◽  
Michael Lübbert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Culture ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Transcriptional Activity ◽  
Target Gene ◽  
Wild Type ◽  
Elevated Expression ◽  
Factor C ◽  
Acute Myeloid

AbstractMutations in the transcription factor C/EBPα are found in ~10% of all acute myeloid leukaemia (AML) cases but the contribution of these mutations to leukemogenesis is incompletely understood. We here use a mouse model of granulocyte progenitors expressing conditionally active HoxB8 to assess the cell biological and molecular activity of C/EBPα-mutations associated with human AML. Both N-terminal truncation and C-terminal AML-associated mutations of C/EBPα substantially altered differentiation of progenitors into mature neutrophils in cell culture. Closer analysis of the C/EBPα-K313-duplication showed expansion and prolonged survival of mutant C/EBPα-expressing granulocytes following adoptive transfer into mice. C/EBPα-protein containing the K313-mutation further showed strongly enhanced transcriptional activity compared with the wild-type protein at certain promoters. Analysis of differentially regulated genes in cells overexpressing C/EBPα-K313 indicates a strong correlation with genes regulated by C/EBPα. Analysis of transcription factor enrichment in the differentially regulated genes indicated a strong reliance of SPI1/PU.1, suggesting that despite reduced DNA binding, C/EBPα-K313 is active in regulating target gene expression and acts largely through a network of other transcription factors. Strikingly, the K313 mutation caused strongly elevated expression of C/EBPα-protein, which could also be seen in primary K313 mutated AML blasts, explaining the enhanced C/EBPα activity in K313-expressing cells.

scholarly journals Single-nucleus RNA-seq and FISH identify coordinated transcriptional activity in mammalian myofibers

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthieu Dos Santos ◽  
Stéphanie Backer ◽  
Benjamin Saintpierre ◽  
Brigitte Izac ◽  
Muriel Andrieu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Transcription Factors ◽  
Neuromuscular Junction ◽  
Heavy Chain ◽  
Transcriptional Activity ◽  
Rna Seq ◽  
Hybrid Fibers ◽  
Adult Mice ◽  
Single Nucleus

Abstract Skeletal muscle fibers are large syncytia but it is currently unknown whether gene expression is coordinately regulated in their numerous nuclei. Here we show by snRNA-seq and snATAC-seq that slow, fast, myotendinous and neuromuscular junction myonuclei each have different transcriptional programs, associated with distinct chromatin states and combinations of transcription factors. In adult mice, identified myofiber types predominantly express either a slow or one of the three fast isoforms of Myosin heavy chain (MYH) proteins, while a small number of hybrid fibers can express more than one MYH. By snRNA-seq and FISH, we show that the majority of myonuclei within a myofiber are synchronized, coordinately expressing only one fast Myh isoform with a preferential panel of muscle-specific genes. Importantly, this coordination of expression occurs early during post-natal development and depends on innervation. These findings highlight a previously undefined mechanism of coordination of gene expression in a syncytium.

scholarly journals Coactivator PC4 Mediates AP-2 Transcriptional Activity and Suppresses ras-Induced Transformation Dependent on AP-2 Transcriptional Interference

1999 ◽  
Vol 19 (1) ◽  
pp. 899-908 ◽  
Author(s):  
Perry Kannan ◽  
Michael A. Tainsky
Keyword(s):  
Gene Expression ◽  
Growth Rate ◽  
Transcription Factors ◽  
Cell Lines ◽  
Transcriptional Activity ◽  
Suppressive Effect ◽  
Transcriptional Coactivator ◽  
Transcriptional Interference ◽  
Mechanism Of Inhibition ◽  
Teratocarcinoma Cells

ABSTRACT ras oncogene-transformed PA-1 human teratocarcinoma cells have abundant AP-2 mRNA but, paradoxically, little AP-2 transcriptional activity. We have previously shown that overexpression of AP-2 in nontumorigenic variants of PA-1 cells results in inhibition of AP-2 activity and induction of tumorigenicity similar to that caused by ras transformation of PA-1 cells. Evidence indicated the existence of a novel mechanism of inhibition of AP-2 activity involving sequestering of transcriptional coactivators. In this study, we found that PC4 is a positive coactivator of AP-2 and can restore AP-2 activity in ras-transformed PA-1 cells. Relative to vector-transfected ras cell lines,ras cell lines stably transfected with and expressing the PC4 cDNA have a diminished growth rate and exhibit a loss of anchorage-independent growth, and they are unable to induce the formation of tumors in nude mice. These data suggest that a transcriptional coactivator, like a tumor suppressor, can have a growth-suppressive effect on cells. Our experiments are the first to show that ras oncogenes and oncogenic transcription factors can induce transformation through effects on the transcription machinery rather than through specific programs of gene expression.

Analysis of transcriptional activity by the Myt1 and Myt1l transcription factors

2018 ◽  
Vol 119 (6) ◽  
pp. 4644-4655 ◽  
Author(s):  
Arkadi Manukyan ◽  
Izabela Kowalczyk ◽  
Tiffany A. Melhuish ◽  
Agata Lemiesz ◽  
David Wotton
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activity

Identification of transcription factors associated with castration-resistance: Is the serum responsive factor a potential therapeutic target?

The Prostate ◽  
2013 ◽  
Vol 73 (7) ◽  
pp. 743-753 ◽  
Author(s):  
Maria Prencipe ◽  
Stephen F. Madden ◽  
Amanda O'Neill ◽  
Gillian O'Hurley ◽  
Aedin Culhane ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Therapeutic Target ◽  
Castration Resistance ◽  
Potential Therapeutic Target ◽  
Factors Associated

scholarly journals Differential regulation of neuronal nicotinic acetylcholine receptor subunit gene promoters by Brn-3 POU family transcription factors

1996 ◽  
Vol 317 (2) ◽  
pp. 419-423 ◽  
Author(s):  
Nathaniel G. N. MILTON ◽  
Alain BESSIS ◽  
Jean-Pierre CHANGEUX ◽  
David S. LATCHMAN
Keyword(s):  
Transcription Factors ◽  
Regulatory Region ◽  
Differential Regulation ◽  
Gene Promoters ◽  
The Novel ◽  
Receptor Subunit ◽  
Subunit Gene ◽  
Related Factors ◽  
Nicotinic Acetylcholine ◽  
Stimulation Of

The regulatory region of the neuronal nicotinic acetylcholine (nACh) receptor α2 subunit gene is activated by the Brn-3b POU family transcription factor but not by the closely related factors Brn-3a and Brn-3c. This pattern of regulation has not previously been observed for other neuronally expressed genes, several of which, such as those encoding α-internexin or SNAP-25, are activated by Brn-3a and Brn-3c but repressed by Brn-3b. The α3 nACh receptor subunit gene is also shown to be activated by Brn-3a but is repressed by Brn-3b and Brn-3c. In contrast, the Brn-3 POU family transcription factors have no effects on either the α7 or β4 nACh receptor subunit genes. The actions of Brn-3b on the α2 subunit are thus in contrast to the inhibitory actions of Brn-3b on several promoters that are activated by Brn-3a. The different actions of the Brn-3 POU factors on the range of nACh receptor genes tested suggests that the novel stimulation of the α2 subunit by Brn-3b is specific to this subunit and not a general feature of nACh receptor genes.

Characterization of interactions between transcription factors and a regulatory region spanning nt −320 to −281 of the HIV-1 LTR in T-lymphoid and non-T-lymphoid cells

2002 ◽  
Vol 9 (1) ◽  
pp. 68-81
Author(s):  
Lloyd A. Pereira ◽  
Melissa J. Churchill ◽  
Andrew G. Elefanty ◽  
Theo Gouskos ◽  
Paul F. Lambert ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Regulatory Region ◽  
Lymphoid Cells ◽  
Hiv 1

scholarly journals Molecular cloning of a novel human cDNA encoding a zinc finger protein that binds to the interleukin-3 promoter.

1994 ◽  
Vol 14 (8) ◽  
pp. 5099-5107 ◽  
Author(s):  
N Koyano-Nakagawa ◽  
J Nishida ◽  
D Baldwin ◽  
K Arai ◽  
T Yokota
Keyword(s):  
T Cell ◽  
Zinc Finger ◽  
Transcriptional Activity ◽  
Regulatory Region ◽  
Jurkat Cells ◽  
Type I ◽  
Dependent Manner ◽  
Cell Leukemia Virus Type ◽  
Transcription Activity ◽  
Interleukin 3

The CT/GC-rich region (-76 to -47) is one transcriptional regulatory region of the interleukin-3 (IL-3) gene which confers basic transcriptional activity and responds to trans-activation by human T-cell leukemia virus type I-encoded Tax. We isolated three types of cDNAs encoding Cys2/His2-type zinc finger proteins that bind to this region. Two were identical to known transcription factors, EGR1 and EGR2, and the other clone, named DB1, encoded a novel protein of 516 amino acids with six zinc finger motifs. DB1 mRNA was present in human tissues, ubiquitously. Two constitutive transcripts of 4.0 and 4.8 kb in length were present in Jurkat cells. Electrophoretic mobility shift assay, with specific antibodies, showed that DB1 constitutively binds to this region whereas EGR1 binds in a T-cell activation-dependent manner. Overexpression of DB1 in Jurkat cells had no detectable effect on the transcription activity of the IL-3 promoter, in a transient-transfection assay. EGR1 and EGR2 increased IL-3 promoter activity when the transfected cells were stimulated with phorbol-12-myristate-13-acetate and A23187. When DB1 was cotransfected with a Tax expression vector, transcription activity of the IL-3 promoter induced by Tax was significantly increased, while EGR1 and EGR2 were without effect. These results suggest that EGR1 has a role in inducible transcription of the IL-3 gene, while DB1 sustains basal transcriptional activity and also cooperates with Tax to activate the IL-3 promoter.

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