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3D-Image analysis platform monitoring relocation of pluripotency genes during reprogramming.

Jost, K. Laurence and Haase, Sebastian and Smeets, Daniel and Schrode, Nadine and Schmiedel, Jörn M. and Bertulat, Bianca and Herzel, Hanspeter and Cremer, Marion and Cardoso, M Cristina (2011):
3D-Image analysis platform monitoring relocation of pluripotency genes during reprogramming.
In: Nucleic acids research, 39 (17), pp. E113-U27, ISSN 1362-4962,
[Online-Edition: http://www.cardoso-lab.org/publications/Jost_2011.pdf],
[Article]

Abstract

Nuclear organization of chromatin is an important level of genome regulation with positional changes of genes occurring during reprogramming. Inherent variability of biological specimens, wide variety of sample preparation and imaging conditions, though pose significant challenges to data analysis and comparison. Here, we describe the development of a computational image analysis toolbox overcoming biological variability hurdles by a novel single cell randomizing normalization. We performed a comparative analysis of the relationship between spatial positioning of pluripotency genes with their genomic activity and determined the degree of similarity between fibroblasts, induced pluripotent stem cells and embryonic stem cells. Our analysis revealed a preferred positioning of actively transcribed Sox2, Oct4 and Nanog away from the nuclear periphery, but not from pericentric heterochromatin. Moreover, in the silent state, we found no common nuclear localization for any of the genes. Our results suggest that the surrounding gene density hinders relocation from an internal nuclear position. Altogether, our data do not support the hypothesis that the nuclear periphery acts as a general transcriptional silencer, rather suggesting that internal nuclear localization is compatible with expression in pluripotent cells but not sufficient for expression in mouse embryonic fibroblasts. Thus, our computational approach enables comparative analysis of topological relationships in spite of stark morphological variability typical of biological data sets.

Item Type: Article
Erschienen: 2011
Creators: Jost, K. Laurence and Haase, Sebastian and Smeets, Daniel and Schrode, Nadine and Schmiedel, Jörn M. and Bertulat, Bianca and Herzel, Hanspeter and Cremer, Marion and Cardoso, M Cristina
Title: 3D-Image analysis platform monitoring relocation of pluripotency genes during reprogramming.
Language: English
Abstract:

Nuclear organization of chromatin is an important level of genome regulation with positional changes of genes occurring during reprogramming. Inherent variability of biological specimens, wide variety of sample preparation and imaging conditions, though pose significant challenges to data analysis and comparison. Here, we describe the development of a computational image analysis toolbox overcoming biological variability hurdles by a novel single cell randomizing normalization. We performed a comparative analysis of the relationship between spatial positioning of pluripotency genes with their genomic activity and determined the degree of similarity between fibroblasts, induced pluripotent stem cells and embryonic stem cells. Our analysis revealed a preferred positioning of actively transcribed Sox2, Oct4 and Nanog away from the nuclear periphery, but not from pericentric heterochromatin. Moreover, in the silent state, we found no common nuclear localization for any of the genes. Our results suggest that the surrounding gene density hinders relocation from an internal nuclear position. Altogether, our data do not support the hypothesis that the nuclear periphery acts as a general transcriptional silencer, rather suggesting that internal nuclear localization is compatible with expression in pluripotent cells but not sufficient for expression in mouse embryonic fibroblasts. Thus, our computational approach enables comparative analysis of topological relationships in spite of stark morphological variability typical of biological data sets.

Journal or Publication Title: Nucleic acids research
Volume: 39
Number: 17
Divisions: 10 Department of Biology > Cell Biology and Epigenetics
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10 Department of Biology
Date Deposited: 25 Jul 2011 12:05
Official URL: http://www.cardoso-lab.org/publications/Jost_2011.pdf
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