scholarly journals SPT6 loss Permits the Transdifferentiation of Keratinocytes into an Intestinal Fate that Recapitulates Barretts Metaplasia

2021 ◽  
Author(s):  
Daniella Vo ◽  
MacKenzie R. Fuller ◽  
Courtney Tindle ◽  
Mahithashree Anandachar ◽  
Soumita Das ◽  
...  
Keyword(s):  
Squamous Epithelium ◽  
Transcription Elongation ◽  
Elongation Factor ◽  
Acid Reflux ◽  
Epidermal Differentiation ◽  
Cell Of Origin ◽  
Profound Impact ◽  
Transcription Elongation Factor ◽  
Human Models ◽  
Stratified Squamous Epithelium

Transient depletion of the transcription elongation factor SPT6 in the keratinocyte has been recently shown to inhibit epidermal differentiation and stratification; instead, they transdifferentiate into a gut-like lineage. We show here that this phenomenon of transdifferentiation recapitulates Barretts metaplasia, the only human pathophysiologic condition in which a stratified squamous epithelium that is injured due to chronic acid reflux is trans-committed into an intestinal fate. The evidence we present here not only pinpoint the keratinocyte as the cell of origin of Barretts metaplasia, but also provide mechanistic insights linking chronic acid injury, downregulation of SPT6, loss of epidermal fate and metaplastic progression. Because Barretts metaplasia in the esophagus (BE) is a pre-neoplastic condition with no preclinical human models, these findings have a profound impact on the modeling Barretts metaplasia-in-a-dish.

Crystal structure of the human transcription elongation factor DSIF hSpt4 subunit in complex with the hSpt5 dimerization interface

2009 ◽  
Vol 425 (2) ◽  
pp. 373-380 ◽  
Author(s):  
Sabine Wenzel ◽  
Berta M. Martins ◽  
Paul Rösch ◽  
Birgitta M. Wöhrl
Keyword(s):  
Crystal Structure ◽  
Escherichia Coli ◽  
Transcription Factor ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Transcription Elongation ◽  
Elongation Factor ◽  
Structural Similarity ◽  
Transcription Elongation Factor

The eukaryotic transcription elongation factor DSIF [DRB (5,6-dichloro-1-β-D-ribofuranosylbenzimidazole) sensitivity-inducing factor] is composed of two subunits, hSpt4 and hSpt5, which are homologous to the yeast factors Spt4 and Spt5. DSIF is involved in regulating the processivity of RNA polymerase II and plays an essential role in transcriptional activation of eukaryotes. At several eukaryotic promoters, DSIF, together with NELF (negative elongation factor), leads to promoter-proximal pausing of RNA polymerase II. In the present paper we describe the crystal structure of hSpt4 in complex with the dimerization region of hSpt5 (amino acids 176–273) at a resolution of 1.55 Å (1 Å=0.1 nm). The heterodimer shows high structural similarity to its homologue from Saccharomyces cerevisiae. Furthermore, hSpt5-NGN is structurally similar to the NTD (N-terminal domain) of the bacterial transcription factor NusG. A homologue for hSpt4 has not yet been found in bacteria. However, the archaeal transcription factor RpoE” appears to be distantly related. Although a comparison of the NusG-NTD of Escherichia coli with hSpt5 revealed a similarity of the three-dimensional structures, interaction of E. coli NusG-NTD with hSpt4 could not be observed by NMR titration experiments. A conserved glutamate residue, which was shown to be crucial for dimerization in yeast, is also involved in the human heterodimer, but is substituted for a glutamine residue in Escherichia coli NusG. However, exchanging the glutamine for glutamate proved not to be sufficient to induce hSpt4 binding.

scholarly journals Members of the SAGA and Mediator complexes are partners of the transcription elongation factor TFIIS

2004 ◽  
Vol 23 (21) ◽  
pp. 4232-4242 ◽  
Author(s):  
Maxime Wery ◽  
Elena Shematorova ◽  
Benoît Van Driessche ◽  
Jean Vandenhaute ◽  
Pierre Thuriaux ◽  
...  
Keyword(s):  
Transcription Elongation ◽  
Elongation Factor ◽  
Transcription Elongation Factor

A functionally divergent transcription elongation factor 1‐like protein in Toxoplasma gondii

FEBS Letters ◽  
2021 ◽  
Author(s):  
Pallabi Mitra ◽  
Abhijit S. Deshmukh ◽  
Sneha Banerjee ◽  
Chittiraju Khandavalli ◽  
Chinmayee Choudhury
Keyword(s):  
Toxoplasma Gondii ◽  
Transcription Elongation ◽  
Elongation Factor ◽  
Transcription Elongation Factor ◽  
Divergent Transcription ◽  
Elongation Factor 1

scholarly journals The Rpb6 Subunit of Fission Yeast RNA Polymerase II Is a Contact Target of the Transcription Elongation Factor TFIIS

2000 ◽  
Vol 20 (4) ◽  
pp. 1263-1270 ◽  
Author(s):  
Akira Ishiguro ◽  
Yasuhisa Nogi ◽  
Koji Hisatake ◽  
Masami Muramatsu ◽  
Akira Ishihama
Keyword(s):  
Rna Polymerase ◽  
Fission Yeast ◽  
Rna Polymerase Ii ◽  
Transcription Elongation ◽  
Elongation Factor ◽  
Direct Interaction ◽  
Temperature Sensitive ◽  
Single Mutation ◽  
Transcription Elongation Factor ◽  
Essential Region

ABSTRACT The Rpb6 subunit of RNA polymerase II is one of the five subunits common to three forms of eukaryotic RNA polymerase. Deletion and truncation analyses of the rpb6 gene in the fission yeastSchizosaccharomyces pombe indicated that Rpb6, consisting of 142 amino acid residues, is an essential protein for cell viability, and the essential region is located in the C-terminal half between residues 61 and 139. After random mutagenesis, a total of 14 temperature-sensitive mutants were isolated, each carrying a single (or double in three cases and triple in one) mutation. Four mutants each carrying a single mutation in the essential region were sensitive to 6-azauracil (6AU), which inhibits transcription elongation by depleting the intracellular pool of GTP and UTP. Both 6AU sensitivity and temperature-sensitive phenotypes of these rpb6 mutants were suppressed by overexpression of TFIIS, a transcription elongation factor. In agreement with the genetic studies, the mutant RNA polymerases containing the mutant Rpb6 subunits showed reduced affinity for TFIIS, as measured by a pull-down assay of TFIIS-RNA polymerase II complexes using a fusion form of TFIIS with glutathioneS-transferase. Moreover, the direct interaction between TFIIS and RNA polymerase II was competed by the addition of Rpb6. Taken together, the results lead us to propose that Rpb6 plays a role in the interaction between RNA polymerase II and the transcription elongation factor TFIIS.

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