Multivalent Role of Human TFIID in Recruiting Elongation Components at the Promoter-Proximal Region for Transcriptional Control

Lymphocytes regulate their responsiveness to IL-2 through the transcriptional control of the IL-2Rα gene, which encodes a component of the high affinity IL-2 receptor. In the mouse IL-2Rα gene this control is exerted via two regulatable elements, a promoter proximal region, and an IL-2–responsive enhancer (IL-2rE) 1.3 kb upstream. In vitro and in vivo functional analysis of the IL-2rE in the rodent thymic lymphoma-derived, CD4−CD8− cell line PC60 demonstrated that three separate elements, sites I, II, and III, were necessary for IL-2 responsiveness; these three sites demonstrate functional cooperation. Site III contains a consensus binding motif for members of the Ets family of transcription factors. Here we demonstrate that Elf-1, an Ets-like protein, binds to site III and participates in IL-2 responsiveness. In vitro site III forms a complex with a protein constitutively present in nuclear extracts from PC60 cells as well as from normal CD4−CD8− thymocytes. We have identified this molecule as Elf-1 according to a number of criteria. The complex possesses an identical electrophoretic mobility to that formed by recombinant Elf-1 protein and is super-shifted by anti–Elf-1 antibodies. Biotinylated IL-2rE probes precipitate Elf-1 from PC60 extracts provided site III is intact and both recombinant and PC60-derived proteins bind with the same relative affinities to different mutants of site III. In addition, by introducing mutations into the core of the site III Ets-like motif and comparing the corresponding effects on the in vitro binding of Elf-1 and the in vivo IL-2rE activity, we provide strong evidence that Elf-1 is directly involved in IL-2 responsiveness. The nature of the functional cooperativity observed between Elf-1 and the factors binding sites I and II remains unresolved; experiments presented here however suggest that this effect may not require direct interactions between the proteins binding these three elements.

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Aberrant gene expression induced by a high fat diet is linked to H3K9 acetylation in the promoter-proximal region

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms ◽

10.1016/j.bbagrm.2021.194691 ◽

2021 ◽

Vol 1864 (3) ◽

pp. 194691

Author(s):

Núria Morral ◽

Sheng Liu ◽

Abass M. Conteh ◽

Xiaona Chu ◽

Yue Wang ◽

...

Keyword(s):

Gene Expression ◽

High Fat Diet ◽

Proximal Region ◽

High Fat ◽

Aberrant Gene Expression ◽

H3k9 Acetylation ◽

Aberrant Gene ◽

Promoter Proximal Region

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Transvection at the End of the Truncated Chromosome in Drosophila melanogaster

Genetics ◽

10.1093/genetics/163.4.1375 ◽

2003 ◽

Vol 163 (4) ◽

pp. 1375-1387

Author(s):

Mikhail Savitsky ◽

Tatyana Kahn ◽

Ekaterina Pomerantseva ◽

Pavel Georgiev

Keyword(s):

Drosophila Melanogaster ◽

Homologous Chromosome ◽

Regulatory Region ◽

Proximal Region ◽

The Other ◽

Upstream Region ◽

Upstream Sequence ◽

Transcription Start ◽

Promoter Proximal Region

Abstract The phenomenon of transvection is well known for the Drosophila yellow locus. Thus enhancers of a promoterless yellow locus in one homologous chromosome can activate the yellow promoter in the other chromosome where the enhancers are inactive or deleted. In this report, we examined the requirements for trans-activation of the yellow promoter at the end of the deficient chromosome. A number of truncated chromosomes ending in different areas of the yellow regulatory region were examined in combination with the promoterless y alleles. We found that trans-activation of the yellow promoter at the end of a deficient chromosome required ∼6 kb of an additional upstream sequence. The nature of upstream sequences affected the strength of transvection: addition of gypsy sequences induced stronger trans-activation than addition of HeT-A or yellow sequences. Only the promoter proximal region (within -158 bp of the yellow transcription start) was essential for trans-activation; i.e., transvection did not require extensive homology in the yellow upstream region. Finally, the yellow enhancers located on the two pairing chromosomes could cooperatively activate one yellow promoter.

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Structural elements in the flexible tail of the co-chaperone p23 coordinate client binding and progression of the Hsp90 chaperone cycle

Nature Communications ◽

10.1038/s41467-021-21063-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Maximilian M. Biebl ◽

Abraham Lopez ◽

Alexandra Rehn ◽

Lee Freiburger ◽

Jannis Lawatscheck ◽

...

Keyword(s):

Proximal Region ◽

Tryptophan Residue ◽

Structural Elements ◽

Physiological Importance ◽

In Vivo Experiments ◽

Cellular Context ◽

Catalytic Loop ◽

Hsp90 Chaperone

AbstractThe co-chaperone p23 is a central part of the Hsp90 machinery. It stabilizes the closed conformation of Hsp90, inhibits its ATPase and is important for client maturation. Yet, how this is achieved has remained enigmatic. Here, we show that a tryptophan residue in the proximal region of the tail decelerates the ATPase by allosterically switching the conformation of the catalytic loop in Hsp90. We further show by NMR spectroscopy that the tail interacts with the Hsp90 client binding site via a conserved helix. This helical motif in the p23 tail also binds to the client protein glucocorticoid receptor (GR) in the free and Hsp90-bound form. In vivo experiments confirm the physiological importance of ATPase modulation and the role of the evolutionary conserved helical motif for GR activation in the cellular context.

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Transcriptional Pausing Caused by NELF Plays a Dual Role in Regulating Immediate-Early Expression of the junB Gene

Molecular and Cellular Biology ◽

10.1128/mcb.02366-05 ◽

2006 ◽

Vol 26 (16) ◽

pp. 6094-6104 ◽

Cited By ~ 73

Author(s):

Masatoshi Aida ◽

Yexi Chen ◽

Koichi Nakajima ◽

Yuki Yamaguchi ◽

Tadashi Wada ◽

...

Keyword(s):

Rna Polymerase Ii ◽

Transcription Initiation ◽

Mrna Level ◽

Proximal Region ◽

Negative Regulation ◽

Immediate Early ◽

Dual Function ◽

Early Expression ◽

Transcriptional Pausing ◽

Promoter Proximal Region

ABSTRACT Human 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole sensitivity-inducing factor (DSIF) and negative elongation factor (NELF) negatively regulate transcription elongation by RNA polymerase II (RNAPII) in vitro. However, the physiological roles of this negative regulation are not well understood. Here, by using a number of approaches to identify protein-DNA interactions in vivo, we show that DSIF- and NELF-mediated transcriptional pausing has a dual function in regulating immediate-early expression of the human junB gene. Before induction by interleukin-6, RNAPII, DSIF, and NELF accumulate in the promoter-proximal region of junB, mainly at around position +50 from the transcription initiation site. After induction, the association of these proteins with the promoter-proximal region continues whereas RNAPII and DSIF are also found in the downstream regions. Depletion of a subunit of NELF by RNA interference enhances the junB mRNA level both before and after induction, indicating that DSIF- and NELF-mediated pausing contributes to the negative regulation of junB expression, not only by inducing RNAPII pausing before induction but also by attenuating transcription after induction. These regulatory mechanisms appear to be conserved in other immediate-early genes as well.

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Estrogen-related receptor alpha (ERRα) is a key regulator of intestinal homeostasis and protects against colitis

Scientific Reports ◽

10.1038/s41598-021-94499-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Allan Tran ◽

Charlotte Scholtes ◽

Mario Songane ◽

Claudia Champagne ◽

Luc Galarneau ◽

...

Keyword(s):

Transcriptional Control ◽

Current Knowledge ◽

Experimental Colitis ◽

Protective Effects ◽

Mitochondrial Energy Metabolism ◽

Receptor Alpha ◽

Cell Counts ◽

Α Diversity ◽

Estrogen Related Receptor

AbstractThe estrogen-related receptor alpha (ERRα) is a primary regulator of mitochondrial energy metabolism, function and dynamics, and has been implicated in autophagy and immune regulation. ERRα is abundantly expressed in the intestine and in cells of the immune system. However, its role in inflammatory bowel disease (IBD) remains unknown. Here, we report a protective role of ERRα in the intestine. We found that mice deficient in ERRα were susceptible to experimental colitis, exhibiting increased colon inflammation and tissue damage. This phenotype was mediated by impaired compensatory proliferation of intestinal epithelial cells (IEC) following injury, enhanced IEC apoptosis and necrosis and reduced mucus-producing goblet cell counts. Longitudinal analysis of the microbiota demonstrated that loss of ERRα lead to a reduction in microbiome α-diversity and depletion of healthy gut bacterial constituents. Mechanistically, ERRα mediated its protective effects by acting within the radio-resistant compartment of the intestine. It promoted disease tolerance through transcriptional control of key genes involved in intestinal tissue homeostasis and repair. These findings provide new insights on the role of ERRα in the gut and extends our current knowledge of nuclear receptors implicated in IBD.

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Role of Plaque Morphology in Altering the Flow Characteristics in Diseased Coronary Artery

Volume 2: Biomedical and Biotechnology ◽

10.1115/imece2012-89268 ◽

2012 ◽

Author(s):

Carlos Moreno ◽

Kiran Bhaganagar

Keyword(s):

Coronary Artery ◽

Nonlinear Response ◽

Flow Characteristics ◽

Proximal Region ◽

Patient Specific ◽

Plaque Morphology ◽

Mean Velocity ◽

Peak Location ◽

The Mean

Patient specific simulations of a single patient based on an accurate representation of the plaque in a diseased coronary artery with 35% stenosis are performed to understand the effect of inlet forcing frequency and amplitude on the wall shear stress (WSS). Numerical simulations are performed with unsteady flow conditions in a laminar regime. The results have revealed that at low amplitudes, WSS is insensitive to forcing frequency and is it in phase with Q. The maximum WSS is observed at the proximal region of the stenosis, and WSS has highest negative values at the peak location of the stenosis. For higher pulsatile amplitude (a > 1.0), WSS exhibits a strong sensitivity with forcing frequencies. At higher forcing frequency the WSS exhibits nonlinear response to the inlet forcing frequency. Furthermore, significant differences in the mean velocity profile are observed during maximum and minimum volumetric flow rates.

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The Mycobacterium tuberculosis sRNA F6 regulates expression of groEL/S

10.1101/2020.07.15.204107 ◽

2020 ◽

Author(s):

Joanna Houghton ◽

Angela Rodgers ◽

Graham Rose ◽

Kristine B. Arnvig

Keyword(s):

Gene Expression ◽

Mycobacterium Tuberculosis ◽

Small Rnas ◽

Transcriptional Control ◽

Cold Shock ◽

Control Of Gene Expression ◽

Rna Biology ◽

Mouse Model Of Infection

ABSTRACTAlmost 140 years after the identification of Mycobacterium tuberculosis as the etiological agent of tuberculosis, important aspects of its biology remain poorly described. Little is known about the role of post-transcriptional control of gene expression and RNA biology, including the role of most of the small RNAs (sRNAs) identified to date. We have carried out a detailed investigation of the M. tuberculosis sRNA, F6, and show it to be dependent on SigF for expression and significantly induced during in vitro starvation and in a mouse model of infection. However, we found no evidence of attenuation of a ΔF6 strain within the first 20 weeks of infection. A further exploration of F6 using in vitro models of infection suggests a role for F6 as a highly specific regulator of the heat shock repressor, HrcA. Our results point towards a role for F6 during periods of low metabolic activity similar to cold shock and associated with nutrient starvation such as that found in human granulomas in later stages of infection.

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Transcriptional control of maladaptive and protective responses in alcoholics: A role of the NF-κB system

Brain Behavior and Immunity ◽

10.1016/j.bbi.2010.12.019 ◽

2011 ◽

Vol 25 ◽

pp. S29-S38 ◽

Cited By ~ 47

Author(s):

Tatjana Yakovleva ◽

Igor Bazov ◽

Hiroyuki Watanabe ◽

Kurt F. Hauser ◽

Georgy Bakalkin

Keyword(s):

Transcriptional Control

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Transcriptional Control of Honey Bee (Apis mellifera) Major Royal Jelly Proteins by 20-Hydroxyecdysone

Insects ◽

10.3390/insects9030122 ◽

2018 ◽

Vol 9 (3) ◽

pp. 122 ◽

Cited By ~ 4

Author(s):

Paul Winkler ◽

Frank Sieg ◽

Anja Buttstedt

Keyword(s):

Gene Expression ◽

Apis Mellifera ◽

Juvenile Hormone ◽

Honey Bee ◽

Honey Bees ◽

Transcriptional Control ◽

Royal Jelly ◽

Adult Worker ◽

Gene Expression Dynamics

One of the first tasks of worker honey bees (Apis mellifera) during their lifetime is to feed the larval offspring. In brief, young workers (nurse bees) secrete a special food jelly that contains a large amount of unique major royal jelly proteins (MRJPs). The regulation of mrjp gene expression is not well understood, but the large upregulation in well-fed nurse bees suggests a tight repression until, or a massive induction upon, hatching of the adult worker bees. The lipoprotein vitellogenin, the synthesis of which is regulated by the two systemic hormones 20-hydroxyecdysone and juvenile hormone, is thought to be a precursor for the production of MRJPs. Thus, the regulation of mrjp expression by the said systemic hormones is likely. This study focusses on the role of 20-hydroxyecdysone by elucidating its effect on mrjp gene expression dynamics. Specifically, we tested whether 20-hydroxyecdysone displayed differential effects on various mrjps. We found that the expression of the mrjps (mrjp1–3) that were finally secreted in large amounts into the food jelly, in particular, were down regulated by 20-hydroxyecdysone treatment, with mrjp3 showing the highest repression value.

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