| 1. |
- Baptista, Ines S. C., et al.
(author)
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Sequence-dependent model of genes with dual s factor preference
- 2022
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In: Biochimica et Biophysica Acta. Gene Regulatory Mechanisms. - : Elsevier. - 1874-9399 .- 1876-4320. ; 1865:3
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Journal article (peer-reviewed)abstract
- Escherichia coli uses sigma factors to quickly control large gene cohorts during stress conditions. While most of its genes respond to a single sigma factor, approximately 5% of them have dual sigma factor preference. The most common are those responsive to both sigma(70), which controls housekeeping genes, and sigma(38), which activates genes during stationary growth and stresses. Using RNA-seq and flow-cytometry measurements, we show that 'sigma(70+38) genes' are nearly as upregulated in stationary growth as 'sigma(38) genes'. Moreover, we find a clear quantitative relationship between their promoter sequence and their response strength to changes in sigma(38) levels. We then propose and validate a sequence dependent model of sigma(70+38) genes, with dual sensitivity to sigma(38) and sigma(70), that is applicable in the exponential and stationary growth phases, as well in the transient period in between. We further propose a general model, applicable to other stresses and sigma factor combinations. Given this, promoters controlling sigma 70+38 genes (and variants) could become important building blocks of synthetic circuits with predictable, sequence-dependent sensitivity to transitions between the exponential and stationary growth phases.
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| 2. |
- Bondesson, Maria, et al.
(author)
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Estrogen receptor signaling during vertebrate development
- 2015
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In: Biochimica et Biophysica Acta. Gene Regulatory Mechanisms. - : Elsevier BV. - 1874-9399 .- 1876-4320. ; 1849:2, s. 142-151
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Research review (peer-reviewed)abstract
- Estrogen receptors are expressed and their cognate ligands produced in all vertebrates, indicative of important and conserved functions. Through evolution estrogen has been involved in controlling reproduction, affecting both the development of reproductive organs and reproductive behavior. This review broadly describes the synthesis of estrogens and the expression patterns of aromatase and the estrogen receptors, in relation to estrogen functions in the developing fetus and child. We focus on the role of estrogens for the development of reproductive tissues, as well as non-reproductive effects on the developing brain. We collate data from human, rodent, bird and fish studies and highlight common and species-specific effects of estrogen signaling on fetal development. Morphological malformations originating from perturbed estrogen signaling in estrogen receptor and aromatase knockout mice are discussed, as well as the clinical manifestations of rare estrogen receptor alpha and aromatase gene mutations in humans.
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| 3. |
- Felletti, Michele, et al.
(author)
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Regulation of the replication initiator DnaA in Caulobacter crescentus
- 2019
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In: Biochimica et Biophysica Acta. Gene Regulatory Mechanisms. - : Elsevier BV. - 1874-9399 .- 1876-4320. ; 1862:7, s. 697-705
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Research review (peer-reviewed)abstract
- The decision to initiate DNA replication is a critical step in the cell cycle of all organisms. In nearly all bacteria, replication initiation requires the activity of the conserved replication initiation protein DnaA. Due to its central role in cell cycle progression, DnaA activity must be precisely regulated. This review summarizes the current state of DnaA regulation in the asymmetrically dividing alpha-proteobacterium Caulobacter crescentus, an important model for bacterial cell cycle studies. Mechanisms will be discussed that regulate DnaA activity and abundance under optimal conditions and in coordination with the asymmetric Caulobacter cell cycle. Furthermore, we highlight recent findings of how regulated DnaA synthesis and degradation collaborate to adjust DnaA abundance under stress conditions. The mechanisms described provide important examples of how DNA replication is regulated in an a-proteobacterium and thus represent an important starting point for the study of DNA replication in many other bacteria. This article is part of a Special Issue entitled: Dynamic gene expression, edited by Prof. Patrick Viollier.
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| 4. |
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| 5. |
- Holmqvist, Erik, 1977-, et al.
(author)
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RNA-binding activity and regulatory functions of the emerging sRNA-binding protein ProQ
- 2020
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In: Biochimica et Biophysica Acta. Gene Regulatory Mechanisms. - : Elsevier BV. - 1874-9399 .- 1876-4320. ; 1863:9
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Research review (peer-reviewed)abstract
- Regulatory small RNAs (sRNAs) ubiquitously impact bacterial physiology through antisense-mediated control of mRNA translation and stability. In Gram negative bacteria, sRNAs often associate with RNA-binding proteins (RBPs), both to gain cellular stability and to enable regulatory efficiency. The Hfq and CsrA proteins were for long the only known global RBPs implicated in sRNA biology. During the last five years, the FinO domain-containing protein ProQ has emerged as another global RBP with a broad spectrum of sRNA and mRNA ligands. This review provides a summary of the current knowledge of enterobacterial ProQ, with a special focus on RNA binding activity, RNA ligand preferences, influence on RNA stability and gene expression, and impact on bacterial physiology. Considering that characterization of ProQ is still in its infancy, we highlight aspects that, when addressed, will provide important clues to the physiological functions and regulatory mechanisms of this globally acting RBP.
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| 6. |
- Köhler, Claudia
(author)
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Epigenetic mechanisms in the endosperm and their consequences for the evolution of flowering plants
- 2011
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In: BBA - Gene Regulatory Mechanisms. - : Elsevier BV. - 1874-9399 .- 1876-4320. ; 1809, s. 438-443
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Journal article (peer-reviewed)abstract
- The sudden rise of angiosperms to ecological dominance was an "abominable mystery" to Charles Darwin, and understanding the underlying evolutionary driving force has remained a scientific challenge since then. The recognition of polyploidization as an important factor for plant speciation is likely to hold a key to this mystery and we will discuss possible mechanisms underlying this phenomenon. Polyploidization raises an immediate reproductive barrier in the endosperm, pointing towards an important but greatly underestimated role of the endosperm in preventing interploidy hybridizations. Parent-of-origin-specific gene expression is largely restricted to the endosperm, providing an explanation for the dosage sensitivity of the endosperm. Here, we review epigenetic mechanisms causing endosperm dosage sensitivity, their possible consequences for raising interploidy and interspecies hybridization barriers and their impact on flowering plant evolution. This article is part of a Special Issue entitled: Epigenetic Control. (C) 2011 Elsevier B.V. All rights reserved.
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| 7. |
- Li, Tianlu, 1988, et al.
(author)
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The mRNA cap-binding protein Cbc1 is required for high and timely expression of genes by promoting the accumulation of gene-specific activators at promoters
- 2016
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In: Biochimica et Biophysica Acta. Gene Regulatory Mechanisms. - : Elsevier BV. - 1874-9399 .- 1876-4320. ; 1859:2, s. 405-419
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Journal article (peer-reviewed)abstract
- The highly conserved Saccharomyces cerevisiae cap-binding protein Cbc1/Sto1 binds mRNA co-transcriptionally and acts as a key coordinator of mRNA fate. Recently, Cbc1 has also been implicated in transcription elongation and pre-initiation complex (PIC) formation. Previously, we described Cbc1 to be required for cell growth under osmotic stress and to mediate osmostress-induced translation reprogramming. Here, we observe delayed global transcription kinetics in cbc1Δ during osmotic stress that correlates with delayed recruitment of TBP and RNA polymerase II to osmo-induced promoters. Interestingly, we detect an interaction between Cbc1 and the MAPK Hog1,which controls most gene expression changes during osmostress, and observe that deletion of CBC1 delays the accumulation of the activator complex Hot1–Hog1 at osmostress promoters. Additionally, CBC1 deletion specifically reduces transcription rates of highly transcribed genes under non-stress conditions, such as ribosomal protein (RP) genes, while having low impact on transcription of weakly expressed genes. For RP genes, we show that recruitment of the specific activator Rap1, and subsequently TBP, to promoters is Cbc1-dependent. Altogether, our results indicate that binding of Cbc1 to the cappedmRNAs is necessary for the accumulation of specific activators as well as PIC components at the promoters of genes whose expression requires high and rapid transcription.
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| 8. |
- Malla, Sandhya, et al.
(author)
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Steering pluripotency and differentiation with N6-methyladenosine RNA modification
- 2019
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In: Biochimica et Biophysica Acta. Gene Regulatory Mechanisms. - : Elsevier. - 1874-9399 .- 1876-4320. ; 1862:3, s. 394-402
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Journal article (peer-reviewed)abstract
- Chemical modifications of RNA provide a direct and rapid way to modulate the existing transcriptome, allowing the cells to adapt rapidly to the changing environment. Among these modifications, N6-methyladenosine (m6A) has recently emerged as a widely prevalent mark of messenger RNA in eukaryotes, linking external stimuli to an intricate network of transcriptional, post-transcriptional and translational processes. m6A modification modulates a broad spectrum of biochemical processes, including mRNA decay, translation and splicing. Both m6A modification and the enzymes that control m6A metabolism are essential for normal development. In this review, we summarized the most recent findings on the role of m6A modification in maintenance of the pluripotency of embryonic stem cells (ESCs), cell fate specification, the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs), and differentiation of stem and progenitor cells.
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| 9. |
- Pan, Gang, et al.
(author)
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Polymorphisms rs55710213 and rs56334587 regulate SCD1 expression by modulating HNF4A binding
- 2021
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In: Biochimica et Biophysica Acta. Gene Regulatory Mechanisms. - : Elsevier. - 1874-9399 .- 1876-4320. ; 1864:8
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Journal article (peer-reviewed)abstract
- The stearoyl-CoA desaturase 1 (SCD1) gene at 10q24.31 encodes the rate limiting enzyme SCD1 that catalyzes the biosynthesis of monounsaturated fatty acids (MUFAs) from saturated fatty acids (SFAs). Dysregulated SCD1 activity has been observed in many human diseases including non-alcoholic fatty liver disease (NAFLD), obesity, hypertension, hyperlipidemia, metabolic syndrome and several types of cancer. HNF4A is a central regulator of glucose and lipid metabolism and previous studies suggested that it is deeply involved in regulating the SCD1 activity in the liver. However, the underlying mechanisms on whether and how SCD1 is regulated by HNF4A have not been explored in detail. In this study, we found that HNF4A regulates SCD1 expression by directly binding to the key regulatory regions in the SCD1 locus. Knocking down of HNF4A significantly downregulated the expression of SCD1. Variants rs55710213 and rs56334587 in intron 5 of SCD1 directly reside in a canonical HNF4A binding site. The GG haplotype of rs55710213 and rs56334587 is associated with decreased SCD1 activity by disrupting the binding of HNF4A, which further decreased the enhancer activity and SCD1 expression. In conclusion, our study demonstrated that SCD1 is directly regulated by HNF4A, which may be helpful in the understanding of the altered metabolic pathways in many diseases associated with dysregulated SCD1 or HNF4A or both.
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