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| 2. |
- Boija, Ann, et al.
(författare)
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CBP Regulates Recruitment and Release of Promoter-Proximal RNA Polymerase II
- 2017
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Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 68:3, s. 491-503.e5
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Tidskriftsartikel (refereegranskat)abstract
- Transcription activation involves RNA polymerase II (Pol II) recruitment and release from the promoter into productive elongation, but how specific chromatin regulators control these steps is unclear. Here, we identify a novel activity of the histone acetyltransferase p300/CREB-binding protein (CBP) in regulating promoter-proximal paused Pol II. We find that Drosophila CBP inhibition results in "dribbling" of Pol II from the pause site to positions further downstream but impedes transcription through the +1 nucleosome genome-wide. Promoters strongly occupied by CBP and GAGA factor have high levels of paused Pol II, a unique chromatin signature, and are highly expressed regardless of cell type. Interestingly, CBP activity is rate limiting for Pol II recruitment to these highly paused promoters through an interaction with TFIIB but for transit into elongation by histone acetylation at other genes. Thus, CBP directly stimulates both Pol II recruitment and the ability to traverse the first nucleosome, thereby promoting transcription of most genes.
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| 3. |
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| 4. |
- Cederholm, Tommy, et al.
(författare)
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Forskaren, samhället och jäv
- 2008
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Ingår i: Läkartidningen. - 0023-7205. ; 105:16, s. 7-1206
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
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| 6. |
- Kahn, Tatyana G., et al.
(författare)
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Interdependence of PRC1 and PRC2 for recruitment to Polycomb Response Elements
- 2016
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 44:21, s. 10132-10149
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Tidskriftsartikel (refereegranskat)abstract
- Polycomb Group (PcG) proteins are epigenetic repressors essential for control of development and cell differentiation. They form multiple complexes of which PRC1 and PRC2 are evolutionary conserved and obligatory for repression. The targeting of PRC1 and PRC2 is poorly understood and was proposed to be hierarchical and involve tri-methylation of histone H3 (H3K27me3) and/or monoubiquitylation of histone H2A (H2AK118ub). Here, we present a strict test of this hypothesis using the Drosophila model. We discover that neither H3K27me3 nor H2AK118ub is required for targeting PRC complexes to Polycomb Response Elements (PREs). We find that PRC1 can bind PREs in the absence of PRC2 but at many PREs PRC2 requires PRC1 to be targeted. We show that one role of H3K27me3 is to allow PcG complexes anchored at PREs to interact with surrounding chromatin. In contrast, the bulk of H2AK118ub is unrelated to PcG repression. These findings radically change our view of how PcG repression is targeted and suggest that PRC1 and PRC2 can communicate independently of histone modifications.
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| 7. |
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| 8. |
- Landberg, Rikard, et al.
(författare)
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Comparison of supercritical carbon dioxide and ethyl acetate extraction of alkylresorcinols from wheat and rye
- 2007
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Ingår i: Journal of Food Composition and Analysis. - : Elsevier BV. - 0889-1575. ; 20:6, s. 534-538
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the application of supercritical carbon dioxide extraction of alkylresorcinols (AR) was quantitatively and qualitatively compared to a commonly used ethyl acetate extraction procedure. No difference in total AR content, relative homolog composition or total extract yield was found between the two extraction methods. Ethyl acetate extraction of intact wheat and rye kernels yielded only 9-20% of the total extract weight obtained with milled samples, but the same amount of alkylresorcinols, showing the benefit of analyzing intact grains whenever it is possible. The major compounds in all extracts (R-f = 0.8) were fatty acids in esterified form, most probably fatty acid alcohol esters. The two different extraction techniques produced comparable results under the conditions used, which suggests that issues other than performance need to be considered when choosing an appropriate technique. (c) 2007 Elsevier Inc. All rights reserved.
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| 9. |
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| 10. |
- Rehman, Humaira, et al.
(författare)
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Effects of endocrine disruptor furan on reproductive physiology of Sprague Dawley rats : An F1 Extended One-Generation Reproductive Toxicity Study (EOGRTS)
- 2020
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Ingår i: Human and Experimental Toxicology. - : SAGE PUBLICATIONS LTD. - 0960-3271 .- 1477-0903. ; 39:8, s. 1079-1094
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated the reproductive toxicity of furan in an Extended One-Generation Reproductive Toxicity Study in rats. Sprague Dawley F0 weaning rats (30 per sex per group) were exposed to furan orally at 0, 1, 2.5, 5, and 10 mg kg(-1) for 10 weeks (males) and 2 weeks (females) and then mated. Results of F0 indicated that in the furan-treated groups (5 mg kg(-1) and 10 mg kg(-1)), body weight (bw) gain decreased during prebreed and gestational period while increased during lactation periods. F0 animals prebreeding exposure resulted in head tilt and foot splay at 10 mg kg(-1). Number of live pups at birth were decreased (p < 0.001) at 10 mg kg(-1). At postnatal day (PND) 70, a significant (p = 0.03) decrease in testosterone levels of male rats and estrogen levels of female rats (p = 0.05) was observed in 10 mg kg(-1) furan-treated group in F1 generation. Luteinizing hormone, follicle-stimulating hormone, and progesterone levels were also reduced, but their reduction was not statistically significant in all groups. In higher dose furan group (10 mg kg(-1)), testicular and ovarian weights were reduced in F1 generation at PND 70, with decreased daily sperm production (p = 0.01) and disturbed estrous cyclicity (p < 0.01). Some histopathological changes were also observed in testis and ovaries in groups whose parents were previously exposed to 10 mg kg(-1) bw of furan group. Based on the above results, it is suggested that exposure to food-based contaminant furan induced remarkable changes in the F0 (parental stage) and F1 (offspring, pubertal, and adult stage) generations of Sprague Dawley rats.
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| 11. |
- Siegbahn, Agneta, et al.
(författare)
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Production of chemokinetic inhibitory factor (CIF) by normal blood and spleen B lymphocytes
- 1986
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Ingår i: Leukemia Research. - 0145-2126 .- 1873-5835. ; 10:2, s. 179-186
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We have recently reported the partial purification and characterization of of a new lymphokine, the heat-labile chemokinetic inhibitory factor (CIF) which inhibits neutrophil movement. We have also shown that this lymphokine is produced and secreted by cultured B-chronic lymphocytic leukaemia (CLL) cells in vitro. The present study shows that highly purified resting normal B lymphocytes from blood and spleen have the capacity to produce CIF spontaneously. After activation with anti-IgM or EBV-infection the lymphocytes produced a number of other factors, heat-stable chemokinetic inhibitory factors and heat-labile chemokinetic enhancing factors. Supernatants from a collection of human B-cell lines representing different stages of B-cell differentiation were also investigated. None of these cell lines produced CIF. The present results show that the production of CIF is not restricted to the malignant B-CLL cell but is also produced by a subset of normal blood and spleen B cells.
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| 12. |
- Zare, Aman, 1987-
(författare)
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Regulation of gene expression in fruit flies : how does it start, and will it be remembered?
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- One of the most distinctive features of eukaryotic chromosomes is the bundling of DNA together with functionally associated RNA and proteins in chromatin. This allows huge amounts of DNA to be packed inside the very tiny space of the nucleus, and alterations in the structure of chromatin enable access to the DNA for transcription (“reading” genes by production of RNA copies). Much of the current knowledge of chromatin structure and regulation comes from studies of Drosophila melanogaster. When the chromatin structure is open the transcription of a gene can start after recruitment of the necessary factors. The main enzyme for gene transcription is Polymerase II (Pol II). For successful gene transcription, Pol II must not only be recruited to the gene’s promoter, but also escape from a pausing state which occurs soon after transcription initiation. CBP/P300 is one of the co-activators involved in transcriptional activation. In the studies this thesis is based upon, my colleagues and I (hereafter we) discovered a new function for CBP in transcription activation. Using high throughput sequencing techniques, we found that CBP directly stimulates recruitment of Pol II to promoters, and facilitates its release from the paused state, enabling progression to the elongation stage of transcription.For cells to remember their identity following division during development, the transcriptional state of genes must be transmitted. Intensively studied players involved in this memory are the Polycomb group (PcG) proteins, responsible for maintaining the repressed state of important developmental genes. The core members are Polycomb repressive complex 1 and 2 (PRC1 and PRC2), which are recruited in flies through poorly known mechanisms to target genes by so-called Polycomb response elements (PREs). Using Drosophila mutant cell lines, we showed that (in contrast to previous models) some PREs can recruit PRC1 even when PRC2 is absent. We also observed that at many PREs, PRC1 is needed for recruitment of PRC2 and concluded that targeting PRC complexes to PREs is a much more flexible and variable process than previously thought.Some phenotypic effects of environmental changes can be transferred to subsequent generations. Previous efforts to identify the mechanisms involved have focused on material (mainly, but not only, DNA) transferred through germ cells. However, organisms’ microbiomes are also transferred to the next generation. Thus, to investigate possible contributions of microbiomes to such transfer, we used fruit flies as the microbiomes they inherit can be easily controlled. We altered some parents’ environmental conditions by lowering the temperature, then grew offspring that received microbiomes from cold-treated and control parents in control conditions and compared their transcriptional patterns. Our results suggest that most of the crosstalk between the microbiome and the fly happens in the gut, and that further investigation of this previously unsuspected mode of inheritance is warranted.
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| 13. |
- Zare, Aman, et al.
(författare)
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The gut microbiome participates in transgenerational inheritance of low temperature responses in Drosophila melanogaster
- 2018
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Ingår i: FEBS Letters. - : John Wiley & Sons. - 0014-5793 .- 1873-3468. ; 592:24, s. 4078-4086
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Tidskriftsartikel (refereegranskat)abstract
- Environmental perturbations induce transcriptional changes, some of which may be inherited even in the absence of the initial stimulus. Previous studies have focused on transfers through the germ-line although microbiota is also passed on to the offspring. Thus, we inspected the involvement of the gut microbiome in transgenerational inheritance of environmental exposures in Drosophila melanogaster. We grew flies in the cold versus control temperatures and compared their transcriptional patterns in both conditions as well as in their offspring. F2 flies grew in control temperature while we controlled their microbiota acquisition from either F1 sets. Transcriptional status of some genes was conserved transgenerationally, and a subset of these genes, mainly expressed in the gut, was transcriptionally dependent on the acquired microbiome. This article is protected by copyright. All rights reserved.
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