scholarly journals The H3.3K27M oncohistone antagonizes reprogramming in Drosophila

PLoS Genetics ◽  
2021 ◽  
Vol 17 (7) ◽  
pp. e1009225
Author(s):  
Kami Ahmad ◽  
Steven Henikoff

Development proceeds by the activation of genes by transcription factors and the inactivation of others by chromatin-mediated gene silencing. In certain cases development can be reversed or redirected by mis-expression of master regulator transcription factors. This must involve the activation of previously silenced genes, and such developmental aberrations are thought to underlie a variety of cancers. Here, we express the wing-specific Vestigial master regulator to reprogram the developing eye, and test the role of silencing in reprogramming using an H3.3K27M oncohistone mutation that dominantly inhibits histone H3K27 trimethylation. We find that production of the oncohistone blocks eye-to-wing reprogramming. CUT&Tag chromatin profiling of mutant tissues shows that H3K27me3 of domains is generally reduced upon oncohistone production, suggesting that a previous developmental program must be silenced for effective transformation. Strikingly, Vg and H3.3K27M synergize to stimulate overgrowth of eye tissue, a phenotype that resembles that of mutations in Polycomb silencing components. Transcriptome profiling of elongating RNA Polymerase II implicates the mis-regulation of signaling factors in overgrowth. Our results demonstrate that growth dysregulation can result from the simple combination of crippled silencing and transcription factor mis-expression, an effect that may explain the origins of oncohistone-bearing cancers.

2020 ◽  
Author(s):  
Kami Ahmad ◽  
Steven Henikoff

AbstractDevelopment proceeds by the activation of genes by transcription factors and the inactivation of others by chromatin-mediated gene silencing. In some cases development can be reversed or redirected by mis-expression of master regulator transcription factors. This must involve the activation of previously silenced genes, and such developmental aberrations are thought to underlie a variety of cancers. Here, we express the wing-specific Vestigial master regulator to reprogram the developing eye, and test the role of silencing in reprogramming using an H3.3K27M oncohistone mutation that dominantly inhibits histone H3K27 trimethylation. We find that expression of the oncohistone blocks eye-to-wing reprogramming. CUT&Tag chromatin profiling of mutant tissues shows that H3K27me3 domains are globally reduced with oncohistone expression, suggesting that previous developmental programs must be silenced for effective transformation. Strikingly, mis-expressed Vg and H3.3K27M synergize to stimulate overgrowth of eye tissue, a phenotype that resembles that of mutations in Polycomb Repressive Complex 1 components. Our results imply that growth dysregulation can result from the simple combination of crippled silencing and transcription factor mis-expression, an effect that may explain the origins of oncohistone-bearing cancers.


1990 ◽  
Vol 10 (12) ◽  
pp. 6335-6347
Author(s):  
E Maldonado ◽  
I Ha ◽  
P Cortes ◽  
L Weis ◽  
D Reinberg

Human transcription factor TFIID, the TATA-binding protein, was partially purified to a form capable of associating stably with the TATA motif of the adenovirus major late promoter. Binding of the human and yeast TFIID to the TATA motif was stimulated by TFIIA. TFIIA is an integral part of a complex capable of binding other transcription factors. A complex formed with human TFIID and TFIIA (DA complex) was specifically recognized by TFIIB. We found that TFIIB activity was contained in a single polypeptide of 32 kDa and that this polypeptide participated in transcription and was capable of binding to the DA complex to form the DAB complex. Formation of the DAB complex required TFIIA, TFIID, and sequences downstream of the transcriptional start site; however, the DA complex could be formed on an oligonucleotide containing only the adenovirus major late promoter TATA motif. Using anti-TFIIB antibodies and reagents that affect the stability of a transcription-competent complex, we found that yeast and human TFIID yielded DAB complexes with different stabilities.


1990 ◽  
Vol 10 (12) ◽  
pp. 6335-6347 ◽  
Author(s):  
E Maldonado ◽  
I Ha ◽  
P Cortes ◽  
L Weis ◽  
D Reinberg

Human transcription factor TFIID, the TATA-binding protein, was partially purified to a form capable of associating stably with the TATA motif of the adenovirus major late promoter. Binding of the human and yeast TFIID to the TATA motif was stimulated by TFIIA. TFIIA is an integral part of a complex capable of binding other transcription factors. A complex formed with human TFIID and TFIIA (DA complex) was specifically recognized by TFIIB. We found that TFIIB activity was contained in a single polypeptide of 32 kDa and that this polypeptide participated in transcription and was capable of binding to the DA complex to form the DAB complex. Formation of the DAB complex required TFIIA, TFIID, and sequences downstream of the transcriptional start site; however, the DA complex could be formed on an oligonucleotide containing only the adenovirus major late promoter TATA motif. Using anti-TFIIB antibodies and reagents that affect the stability of a transcription-competent complex, we found that yeast and human TFIID yielded DAB complexes with different stabilities.


Plants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 578 ◽  
Author(s):  
Ulrike Zentgraf ◽  
Jasmin Doll

Leaf senescence is an integral part of plant development aiming at the remobilization of nutrients and minerals out of the senescing tissue into developing parts of the plant. Sequential as well as monocarpic senescence maximize the usage of nitrogen, mineral, and carbon resources for plant growth and the sake of the next generation. However, stress-induced premature senescence functions as an exit strategy to guarantee offspring under long-lasting unfavorable conditions. In order to coordinate this complex developmental program with all kinds of environmental input signals, complex regulatory cues have to be in place. Major changes in the transcriptome imply important roles for transcription factors. Among all transcription factor families in plants, the NAC and WRKY factors appear to play central roles in senescence regulation. In this review, we summarize the current knowledge on the role of WRKY factors with a special focus on WRKY53. In contrast to a holistic multi-omics view we want to exemplify the complexity of the network structure by summarizing the multilayer regulation of WRKY53 of Arabidopsis.


1999 ◽  
Vol 77 (4) ◽  
pp. 257-264 ◽  
Author(s):  
Benoit Coulombe

The DNA wrapping model of transcription stipulates that DNA bending and wrapping around RNA polymerase causes an unwinding of the DNA helix at the enzyme catalytic center that stimulates strand separation prior to initiation and during transcript elongation. Recent experiments with mammalian RNA polymerase II indicate the significance of DNA bending and wrapping in transcriptional mechanisms. These findings have important implications in our understanding of the role of the general transcription factors in transcriptional initiation and the mechanisms underlying transcriptional regulation.Key words: mRNA synthesis, transcription initiation, RNA polymerase II, DNA wrapping, general transcription factors.


Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 308
Author(s):  
Konstantinos Vlachonasios ◽  
Stylianos Poulios ◽  
Niki Mougiou

Transcription of protein-encoding genes starts with forming a pre-initiation complex comprised of RNA polymerase II and several general transcription factors. To activate gene expression, transcription factors must overcome repressive chromatin structure, which is accomplished with multiprotein complexes. One such complex, SAGA, modifies the nucleosomal histones through acetylation and other histone modifications. A prototypical histone acetyltransferase (HAT) known as general control non-repressed protein 5 (GCN5), was defined biochemically as the first transcription-linked HAT with specificity for histone H3 lysine 14. In this review, we analyze the components of the putative plant SAGA complex during plant evolution, and current knowledge on the biological role of the key components of the HAT module, GCN5 and ADA2b in plants, will be summarized.


Pneumologie ◽  
2012 ◽  
Vol 66 (06) ◽  
Author(s):  
HM Al-Tamari ◽  
M Eschenhagen ◽  
A Schmall ◽  
R Savai ◽  
HA Ghofrani ◽  
...  

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