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

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.

scholarly journals Differential Binding of the Transcription Factors Sp1, AP-1, and NFI to the Promoter of the Human α5 Integrin Gene Dictates Its Transcriptional Activity

2009 ◽  
Vol 50 (1) ◽  
pp. 57 ◽  
Author(s):  
Marie-E`ve Gingras ◽  
Be´ne´dicte Masson-Gadais ◽  
Karine Zaniolo ◽  
Steeve Leclerc ◽  
Re´gen Drouin ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activity ◽  
Integrin Gene ◽  
Differential Binding

scholarly journals Highly sensitive control of transcriptional activity by factor heterodimerization

1994 ◽  
Vol 301 (1) ◽  
pp. 9-12 ◽  
Author(s):  
S Swillens ◽  
I Pirson
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
High Sensitivity ◽  
Biochemical Control ◽  
Cellular Functions ◽  
Effector Molecules ◽  
Highly Sensitive ◽  
New Type ◽  
Very High

Several molecular mechanisms have been proposed to explain highly sensitive controls of cellular functions by effector molecules. Here we study an equilibrium model describing the regulation of transcriptional activity through the heterodimerization of transcription factors. We demonstrate that this model involves a new type of biochemical control which accounts for a very high sensitivity.

scholarly journals TiPARP forms nuclear condensates to degrade HIF-1α and suppress tumorigenesis

2020 ◽  
Vol 117 (24) ◽  
pp. 13447-13456 ◽  
Author(s):  
Lu Zhang ◽  
Ji Cao ◽  
Longying Dong ◽  
Hening Lin
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activity ◽  
Nuclear Bodies ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Adp Ribosylation ◽  
Activation Of Transcription ◽  
Xenograft Models ◽  
Adp Ribosyltransferase ◽  
Feedback Regulator

Precisely controlling the activation of transcription factors is crucial for physiology. After a transcription factor is activated and carries out its transcriptional activity, it also needs to be properly deactivated. Here, we report a deactivation mechanism of HIF-1 and several other oncogenic transcription factors. HIF-1 promotes the transcription of an ADP ribosyltransferase, TiPARP, which serves to deactivate HIF-1. Mechanistically, TiPARP forms distinct nuclear condensates or nuclear bodies in an ADP ribosylation-dependent manner. The TiPARP nuclear bodies recruit both HIF-1α and an E3 ubiquitin ligase HUWE1, which promotes the ubiquitination and degradation of HIF-1α. Similarly, TiPARP promotes the degradation of c-Myc and estrogen receptor. By suppressing HIF-1α and other oncogenic transcription factors, TiPARP exerts strong antitumor effects both in cell culture and in mouse xenograft models. Our work reveals TiPARP as a negative-feedback regulator for multiple oncogenic transcription factors, provides insights into the functions of protein ADP-ribosylation, and suggests activating TiPARP as an anticancer strategy.

scholarly journals Allosteric deactivation of PIFs and EIN3 by microproteins in light control of plant development

2020 ◽  
Vol 117 (31) ◽  
pp. 18858-18868 ◽  
Author(s):  
Qingqing Wu ◽  
Kunyan Kuang ◽  
Mohan Lyu ◽  
Yan Zhao ◽  
Yue Li ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activity ◽  
Environmental Changes ◽  
Protein Complexes ◽  
Binding Capacity ◽  
Negative Control ◽  
Light Responses ◽  
Developmental Transitions ◽  
Evolutionarily Conserved ◽  
Target Molecules

Buried seedlings undergo dramatic developmental transitions when they emerge from soil into sunlight. As central transcription factors suppressing light responses, PHYTOCHROME-INTERACTING FACTORs (PIFs) and ETHYLENE-INSENSITIVE 3 (EIN3) actively function in darkness and must be promptly repressed upon light to initiate deetiolation. Microproteins are evolutionarily conserved small single-domain proteins that act as posttranslational regulators in eukaryotes. Although hundreds to thousands of microproteins are predicted to exist in plants, their target molecules, biological roles, and mechanisms of action remain largely unknown. Here, we show that two microproteins, miP1a and miP1b (miP1a/b), are robustly stimulated in the dark-to-light transition.miP1a/bare primarily expressed in cotyledons and hypocotyl, exhibiting tissue-specific patterns similar to those ofPIFs andEIN3. We demonstrate that PIFs and EIN3 assemble functional oligomers by self-interaction, while miP1a/b directly interact with and disrupt the oligomerization of PIFs and EIN3 by forming nonfunctional protein complexes. As a result, the DNA binding capacity and transcriptional activity of PIFs and EIN3 are predominantly suppressed. These biochemical findings are further supported by genetic evidence. miP1a/b positively regulate photomorphogenic development, and constitutively expressingmiP1a/brescues the delayed apical hook unfolding and cotyledon development of plants overexpressingPIFs andEIN3. Our study reveals that microproteins provide a temporal and negative control of the master transcription factors' oligomerization to achieve timely developmental transitions upon environmental changes.

scholarly journals Co-activator activator (CoAA) prevents the transcriptional activity of Runt domain transcription factors

2009 ◽  
Vol 108 (2) ◽  
pp. 378-387 ◽  
Author(s):  
Xiaodong Li ◽  
Luke H. Hoeppner ◽  
Eric D. Jensen ◽  
Rajaram Gopalakrishnan ◽  
Jennifer J. Westendorf
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activity ◽  
Runt Domain
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