1,354,530 research outputs found
A lncRNA-mediated interaction between Snail and Ezh2 governs epigenetic modifications causal to EMT of the hepatocyte
No full textA lncRNA-mediated interaction between Snail and Ezh2 governs epigenetic modifications causal to EMT of the hepatocyte
Cecilia Battistelli1, Carla Cicchini1, Laura Santangelo1, Anna Tramontano2, Laura Amicone1 and Marco Tripodi1
1Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Rome, Italy
2Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Physics, Sapienza University of Rome, Rome, Italy
Co-authors
Epithelial-to-Mesenchymal Transition (EMT) and the reverse Mesenchymal-to-Epithelial Transition (MET) are manifestations of cellular plasticity that imply a dynamic and profound gene expression reprogramming. We previously demonstrated that the balance between two transcriptional factors, Snail (EMT “master factor) and HNF4α (MET “master” factor), able to reciprocally repress their own expression, ultimately influences the outcome of the transition between the mesenchymal/ undifferentiated and the epithelial/differentiated phenotype. This necessarily implies that these master factors act in a much more complex macromolecular systems, able to direct and modulate a whole transcriptional profile. Starting from the working hypothesis that a transcriptional factor sufficient to trigger and drive EMT might be endowed with the capacity to locally impact chromatin modifications causal to its repressive role, we investigated on how chromatin modifiers instrumental to Snail repressive activity are recruited to its specific sites. We found that a long non-coding RNA mediates a physical interaction between Snail and EZH2, enzymatic subunit of the Polycomb Repressive Complex 2 (PRC2) and the main writer of chromatin repressive marks and demonstrated that a tripartite Snail/lncRNA/EZH2 complex is causal for the execution of a full EMT of hepatocytes.
2006-Cicchini C, et al. J Cell Physiol. Oct; 209(1):230-8.
2011- Santangelo L, et al. Hepatology Jun;53(6):2063-74
2012-Garibaldi F, et al Cell Death and Differentiation. Jun;19(6):937-46.
2015-Cicchini C, et al. Liver Int. Apr 25. doi: 10.1111/liv.12577.
2015-Cicchini C, et al. BBA GRM Volume 1849, Issue 8, August, Pages 919–929
The lncRNA HOTAIR links the repressor Snail to epigenetic modifications of specific genomic sites in Epithelial-to-Mesenchymal Transition
No full textThe lncRNA HOTAIR links the repressor Snail to epigenetic modifications of specific genomic sites in Epithelial-to-Mesenchymal Transition
Cecilia Battistelli 1,§, Carla Cicchini 1,§,, Laura Santangelo 1, Anna Tramontano 2, Marco Tripodi 1,3
1Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Rome, Italy
2Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Physics, Sapienza University of Rome, Rome, Italy
3National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy.
§Co-first authors.
Co-corresponding authors
The transcription factor Snail is a master regulator of cellular identity and Epithelial-to-Mesenchymal Transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail specific binding sites is unclear. Here we report that the long non-coding (lnc)RNA HOTAIR mediates a physical interaction between Snail and EZH2, enzymatic subunit of the Polycomb Repressive Complex 2 (PRC2) and main writer of chromatin repressive marks. The Snail repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate a lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT
transpyloric prolapse of a gastric carcinoma arising from a peduncolated hyperplastic polyp
No full textBiotin-tagged cDNA expression libraries displayed on lambda phage: a new tool for the selection of natural protein ligands
No full textcDNA expression libraries displayed on lambda phage have been successfully employed to identify partners involved in antibody-antigen, protein- protein and DNA-protein interactions and represent a novel approach to functional genomics. However, as in all other cDNA expression libraries based on fusion to a carrier polypeptide, a major issue of this system is the absence of control over the translation frame of the cDNA. As a consequence, a large number of clones will contain lambda D/cDNA fusions, resulting in the foreign sequence being translated on alternative reading frames. Thus, many phage will not display natural proteins, but could be selected, as they mimic the binding properties of the real ligand, and will hence interfere with the selection outcome. Here we describe a novel lambda vector for display of exogenous peptides at the C-terminus of the capsid D protein. In this vector, translation of fusion peptides in the correct reading frame allows efficient in vivo biotinylation of the chimeric phage during amplification. Using this vector system we constructed three libraries from human hepatoma cells, mouse hepatocytic MMH cells and from human brain. Clones containing open reading frames (ORFs) were rapidly selected by streptavidin affinity chromatography, leading to biological repertoires highly enriched in natural polypeptides. We compared the selection outcome of two independent experiments performed using an anti-GAP-43 monoclonal antibody on the human brain cDNA library before and after ORF enrichment. A significant increase in the efficiency of identification of natural target peptides with very little background of false-positive clones was observed in the latter case
Spatiotemporal filtering and motion illusions
No full textSpatiotemporal filtering and motion illusion
"Non-retinotopic processing" in Ternus motion displays modeled by spatiotemporal filters
No full textRecently, M. Boi, H. Ogmen, J. Krummenacher, T. U. Otto, & M. H. Herzog (2009) reported a fascinating visual effect, where the direction of apparent motion was disambiguated by cues along the path of apparent motion, the Ternus-Pikler group motion, even though no actual movement occurs in this stimulus. They referred to their study as a "litmus test" to distinguish "non-retinotopic" (motion-based) from "retinotopic" (retina-based) image processing. We adapted the test to one with simple grating stimuli that could be more readily modeled and replicated their psychophysical results quantitatively with this stimulus. We then modeled our experiments in 3D (x, y, t) Fourier space and demonstrated that the observed perceptual effects are readily accounted for by integration of information within a detector that is oriented in space and time, in a similar way to previous explanations of other motion illusions. This demonstration brings the study of Boi et al. into the more general context of perception of moving objects
Shifts in spatial attention affect the perceived duration of events
No full textWe investigated the relationship between attention and perceived duration of visual events with a double-task paradigm. The primary task was to discriminate the size change of a 2 degree circle presented 10 degrees left, right, above, or below fixation; the secondary task was to judge the temporal separation (from 133 ms to 633 ms) of two equiluminant horizontal bars (10 deg x 2 deg) briefly flashed 12 degrees above or below fixation. The stimulus onset asynchrony (SOA) between primary and secondary task ranged from -1300 ms to +1000 ms. Temporal intervals in proximity of the onset of the primary task stimuli were perceived strongly compressed by up to 40%. The effect was proportional to the size of the interval with a maximum effect at 100 ms SOA. Control experiments show that neither primary-task difficulty, nor the type of primary task discrimination (form or motion, or equiluminant or luminance contrast) nor spatial congruence between primary and secondary task alter the effect. Interestingly, the compression occurred only when the intervals are marked by bars presented in separated spatial locations: when the interval is marked by two bars flashed in the same spatial position no temporal distortion was found. These data indicate that attention can alter perceived duration when the brain has to compare the passage of time at two different spatial positions, corroborating earlier findings that mechanisms of time perception may monitor separately the various spatial locations possibly at high level of analysis
"MOLECULAR MECHANISM CONTROLLING EMT/MET OSCILLATIONS AND HEPATOCYTE DIFFERENTIATION OF RESIDENT LIVER STEM CELLS (RLSCS)".
No full textSelected presentation from submitted (poster) abstracts
The influence of estrogen on hepatic cholesterol metabolism and biliary lipid secretion in rats fed fish oil
No full textCorrelation between chromogranin-A expression and pathological variables in human colon carcinoma
No full textBackground: The possible association between neuroendocrine pattern and cancer prognosis could have substantial clinical implications, but the studies performed have generated conflicting results. As chromogranin-A (CGA) and dense-core granules are expressed concordantly, CGA expression may be used as a marker for cells expressing the complete neuroendocrine cell phenotype. Materials and Methods: Fifty-six patients with primary colon carcinoma who underwent potentially curative surgery were analyzed. For immunohistochemical study a monoclonal antibody specific for human chromogranin A was used. The tumor was considered positive when the number of CGA cells was higher than 10% in the section. The relation between CGA-positivity and depth of parietal invasion, lymph-node status and differentiation grade was examined. Results: We observed positive immunostaining in 22 cases out of 56 (39.3%). Significant association was found between CGA-positivity and lymph-node metastasis. Conclusion: CGA overexpression could reflect a more aggressive tumor. If our results are confirmed, we should consider the CGA + colon cancer patients at risk for lymph-node disease and therefore include them in a adjuvant chemotherapeutic protocol
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