scholarly journals Global regulation of heterochromatin spreading by Leo1

Open Biology ◽  
2015 ◽  
Vol 5 (5) ◽  
pp. 150045 ◽  
Author(s):  
Laure Verrier ◽  
Francesca Taglini ◽  
Ramon R. Barrales ◽  
Shaun Webb ◽  
Takeshi Urano ◽  
...  

Heterochromatin plays important roles in eukaryotic genome regulation. However, the repressive nature of heterochromatin combined with its propensity to self-propagate necessitates robust mechanisms to contain heterochromatin within defined boundaries and thus prevent silencing of expressed genes. Here we show that loss of the PAF complex (PAFc) component Leo1 compromises chromatin boundaries, resulting in invasion of heterochromatin into flanking euchromatin domains. Similar effects are seen upon deletion of other PAFc components, but not other factors with related functions in transcription-associated chromatin modification, indicating a specific role for PAFc in heterochromatin regulation. Loss of Leo1 results in reduced levels of H4K16 acetylation at boundary regions, while tethering of the H4K16 acetyltransferase Mst1 to boundary chromatin suppresses heterochromatin spreading in leo1Δ cells, suggesting that Leo1 antagonises heterochromatin spreading by promoting H4K16 acetylation. Our findings reveal a previously undescribed role for PAFc in regulating global heterochromatin distribution.

2012 ◽  
Vol 209 (11) ◽  
pp. 2099-2111 ◽  
Author(s):  
Katharina L. Willmann ◽  
Sara Milosevic ◽  
Siim Pauklin ◽  
Kerstin-Maike Schmitz ◽  
Gopinath Rangam ◽  
...  

Antibody diversification requires the DNA deaminase AID to induce DNA instability at immunoglobulin (Ig) loci upon B cell stimulation. For efficient cytosine deamination, AID requires single-stranded DNA and needs to gain access to Ig loci, with RNA pol II transcription possibly providing both aspects. To understand these mechanisms, we isolated and characterized endogenous AID-containing protein complexes from the chromatin of diversifying B cells. The majority of proteins associated with AID belonged to RNA polymerase II elongation and chromatin modification complexes. Besides the two core polymerase subunits, members of the PAF complex, SUPT5H, SUPT6H, and FACT complex associated with AID. We show that AID associates with RNA polymerase-associated factor 1 (PAF1) through its N-terminal domain, that depletion of PAF complex members inhibits AID-induced immune diversification, and that the PAF complex can serve as a binding platform for AID on chromatin. A model is emerging of how RNA polymerase II elongation and pausing induce and resolve AID lesions.


2009 ◽  
Vol 29 (17) ◽  
pp. 4852-4863 ◽  
Author(s):  
Ying Liu ◽  
Linda Warfield ◽  
Chao Zhang ◽  
Jie Luo ◽  
Jasmina Allen ◽  
...  

ABSTRACT The Saccharomyces cerevisiae kinase Bur1 is involved in coupling transcription elongation to chromatin modification, but not all important Bur1 targets in the elongation complex are known. Using a chemical genetics strategy wherein Bur1 kinase was engineered to be regulated by a specific inhibitor, we found that Bur1 phosphorylates the Spt5 C-terminal repeat domain (CTD) both in vivo and in isolated elongation complexes in vitro. Deletion of the Spt5 CTD or mutation of the Spt5 serines targeted by Bur1 reduces recruitment of the PAF complex, which functions to recruit factors involved in chromatin modification and mRNA maturation to elongating polymerase II (Pol II). Deletion of the Spt5 CTD showed the same defect in PAF recruitment as rapid inhibition of Bur1 kinase activity, and this Spt5 mutation led to a decrease in histone H3K4 trimethylation. Brief inhibition of Bur1 kinase activity in vivo also led to a significant decrease in phosphorylation of the Pol II CTD at Ser-2, showing that Bur1 also contributes to Pol II Ser-2 phosphorylation. Genetic results suggest that Bur1 is essential for growth because it targets multiple factors that play distinct roles in transcription.


Author(s):  
Robert Pfaller

Starting from a passage from Slavoj Žižek`s brilliant book The Sublime Object of Ideology, the very passage on canned laughter that gave such precious support for the development of the theory of interpassivity, this chapter examines a question that has proved indispensable for the study of interpassivity: namely, what does it mean for a theory to proceed by examples? What is the specific role of the example in certain example-friendly theories, for example in Žižek’s philosophy?


Ergodesign ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 3-18
Author(s):  
Marijam Arpentieva

The article discusses the current problems of the theory and practice of archetypal branding, analyzes the problems of archetypal branding from the perspective of ergonomic support for marketing research. In the framework of modern ergonomics, one of the tasks of its development is the ergonomic support of marketing research, including research on the development and evaluation of the effectiveness and productivity of the brand. A brand that is developed by marketers in accordance with a particular archetype or a specific role model can not only gain consumer recognition, but also help them formulate a way to express themselves. A role model in terms of the ergonomic support of marketing research can be used to develop a brand strategy: it represents an image that reflects a person’s ideas about a desirable role in the community. The client seeks not only to demonstrate this image to people, but also to use it in order to support and transform his own identity. At the same time, role models, unlike archetypal structures, practices and theorists from the standpoint of ergonomic support of marketing research typologize, based directly on a comparison with the leading motives of life and consumption. Role models correspond to different consumption situations, without contradicting the specific cultural and historical context. From the position of ergonomic support of marketing research, they should and can be used as functions specific to a given community, region, and time, as well as transcultural or supercultural structures that reflect one or another pole of the archetype in a particular cultural and historical environment.


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