Chromatin decondensation and nuclear softening accompany Nanog downregulation in embryonic stem cells

Kevin J. Chalut, Markus Höpfler, Franziska Lautenschläger, Lars Boyde, Chii Jou Chan, Andrew Ekpenyong, Alfonso Martinez-Arias, Jochen Guck

Research output: Contribution to journalArticle

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Abstract

The interplay between epigenetic modification and chromatin compaction is implicated in the regulation of gene expression, and it comprises one of the most fascinating frontiers in cell biology. Although a complete picture is still lacking, it is generally accepted that the differentiation of embryonic stem (ES) cells is accompanied by a selective condensation into heterochromatin with concomitant gene silencing, leaving access only to lineage-specific genes in the euchromatin. ES cells have been reported to have less condensed chromatin, as they are capable of differentiating into any cell type. However, pluripotency itself - even prior to differentiation - is a split state comprising a naïve state and a state in which ES cells prime for differentiation. Here, we show that naïve ES cells decondense their chromatin in the course of downregulating the pluripotency marker Nanog before they initiate lineage commitment. We used fluorescence recovery after photobleaching, and histone modification analysis paired with a novel, to our knowledge, optical stretching method, to show that ES cells in the naïve state have a significantly stiffer nucleus that is coupled to a globally more condensed chromatin state. We link this biophysical phenotype to coinciding epigenetic differences, including histone methylation, and show a strong correlation of chromatin condensation and nuclear stiffness with the expression of Nanog. Besides having implications for transcriptional regulation and embryonic cell sorting and suggesting a putative mechanosensing mechanism, the physical differences point to a system-level regulatory role of chromatin in maintaining pluripotency in embryonic development.

Original languageEnglish
Pages (from-to)2060-2070
Number of pages11
JournalBiophysical Journal
Volume103
Issue number10
DOIs
StatePublished - Nov 21 2012
Externally publishedYes

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Embryonic Stem Cells
Chromatin
Down-Regulation
Epigenomics
Histone Code
Euchromatin
Fluorescence Recovery After Photobleaching
Heterochromatin
Gene Expression Regulation
Gene Silencing
Histones
Methylation
Embryonic Development
Cell Biology
Cell Differentiation
Phenotype
Genes

All Science Journal Classification (ASJC) codes

  • Biophysics

Cite this

Chalut, K. J., Höpfler, M., Lautenschläger, F., Boyde, L., Chan, C. J., Ekpenyong, A., ... Guck, J. (2012). Chromatin decondensation and nuclear softening accompany Nanog downregulation in embryonic stem cells. Biophysical Journal, 103(10), 2060-2070. https://doi.org/10.1016/j.bpj.2012.10.015

Chromatin decondensation and nuclear softening accompany Nanog downregulation in embryonic stem cells. / Chalut, Kevin J.; Höpfler, Markus; Lautenschläger, Franziska; Boyde, Lars; Chan, Chii Jou; Ekpenyong, Andrew; Martinez-Arias, Alfonso; Guck, Jochen.

In: Biophysical Journal, Vol. 103, No. 10, 21.11.2012, p. 2060-2070.

Research output: Contribution to journalArticle

Chalut, KJ, Höpfler, M, Lautenschläger, F, Boyde, L, Chan, CJ, Ekpenyong, A, Martinez-Arias, A & Guck, J 2012, 'Chromatin decondensation and nuclear softening accompany Nanog downregulation in embryonic stem cells', Biophysical Journal, vol. 103, no. 10, pp. 2060-2070. https://doi.org/10.1016/j.bpj.2012.10.015
Chalut, Kevin J. ; Höpfler, Markus ; Lautenschläger, Franziska ; Boyde, Lars ; Chan, Chii Jou ; Ekpenyong, Andrew ; Martinez-Arias, Alfonso ; Guck, Jochen. / Chromatin decondensation and nuclear softening accompany Nanog downregulation in embryonic stem cells. In: Biophysical Journal. 2012 ; Vol. 103, No. 10. pp. 2060-2070.
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