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

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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Chalut KJ,Höpfler M,Lautenschläger F,Boyde L,Chan CJ,Ekpenyong A,Martinez-Arias A,Guck J

doi

10.1016/j.bpj.2012.10.015

subject

Has Abstract

pub_date

2012-11-21 00:00:00

pages

2060-70

issue

10

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(12)01120-4

journal_volume

103

pub_type

杂志文章
  • Ba2+ release from soda glass modifies single maxi K+ channel activity in patch clamp experiments.

    abstract::Glasses used to fabricate patch pipettes may release components which affect ion channels (Cota, G., and C.M. Armstrong. 1988. Biophys. J. 53:107-109; Furman, R.E., and J.C. Tanaka. 1988. Biophys. J. 53:287-292; Rojas, L., and C. Zuazaga. 1988. Neurosci. Lett. 88:39-44). The gating properties of maxi K+ channels from ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(91)82127-0

    authors: Copello J,Simon B,Segal Y,Wehner F,Ramanujam VM,Alcock N,Reuss L

    更新日期:1991-10-01 00:00:00

  • 19F nuclear magnetic resonance investigation of stereoselective binding of isoflurane to bovine serum albumin.

    abstract::Whether proteins or lipids are the primary target sites for general anesthetic action has engendered considerable debate. Recent in vivo studies have shown that the S(+) and R(-) enantiomers of isoflurane are not equipotent, implying involvement of proteins. Bovine serum albumin (BSA), a soluble protein devoid of lipi...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(96)79599-1

    authors: Xu Y,Tang P,Firestone L,Zhang TT

    更新日期:1996-01-01 00:00:00

  • Fragmentation is crucial for the steady-state dynamics of actin filaments.

    abstract::Despite the recognition that actin filaments are important for numerous cellular processes, and decades of investigation, the dynamics of in vitro actin filaments are still not completely understood. Here, we follow the time evolution of the length distribution of labeled actin reporter filaments in an unlabeled F-act...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2011.07.009

    authors: Schmoller KM,Niedermayer T,Zensen C,Wurm C,Bausch AR

    更新日期:2011-08-17 00:00:00

  • Detection of jumps in single-channel data containing subconductance levels.

    abstract::Detection algorithms are widely used for the analysis of single-channel data because they remove the background noise from the measured current signal and reconstruct the noise-free time series. Standard detection algorithms assume channels switching only between zero and full conductance. Many types of channels, howe...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(94)80614-9

    authors: Draber S,Schultze R

    更新日期:1994-10-01 00:00:00

  • A probability density approach to modeling local control of calcium-induced calcium release in cardiac myocytes.

    abstract::We present a probability density approach to modeling localized Ca2+ influx via L-type Ca2+ channels and Ca2+-induced Ca2+ release mediated by clusters of ryanodine receptors during excitation-contraction coupling in cardiac myocytes. Coupled advection-reaction equations are derived relating the time-dependent probabi...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.106.099861

    authors: Williams GS,Huertas MA,Sobie EA,Jafri MS,Smith GD

    更新日期:2007-04-01 00:00:00

  • Electron-nuclear double resonance and hyperfine sublevel correlation spectroscopic studies of flavodoxin mutants from Anabaena sp. PCC 7119.

    abstract::The influence of the amino acid residues surrounding the flavin ring in the flavodoxin of the cyanobacterium Anabaena PCC 7119 on the electron spin density distribution of the flavin semiquinone was examined in mutants of the key residues Trp(57) and Tyr(94) at the FMN binding site. Neutral semiquinone radicals of the...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(99)77017-7

    authors: Medina M,Lostao A,Sancho J,Gómez-Moreno C,Cammack R,Alonso PJ,Martínez JI

    更新日期:1999-09-01 00:00:00

  • Emerging Allosteric Mechanism of EGFR Activation in Physiological and Pathological Contexts.

    abstract::Protein kinases are key players in signal transduction pathways where they are crafted into two functional states. In response to growth factor binding stimulus, epidermal growth factor receptor (EGFR), which is physiologically populated in an autoinhibited inactive state, becomes active. Here, we outline a simple all...

    journal_title:Biophysical journal

    pub_type: 杂志文章,评审

    doi:10.1016/j.bpj.2019.05.021

    authors: Tsai CJ,Nussinov R

    更新日期:2019-07-09 00:00:00

  • Characterization of the sperm-induced calcium wave in Xenopus eggs using confocal microscopy.

    abstract::We have used confocal microscopy to examine the [Ca2+]i increase in the albino eggs of the frog Xenopus laevis after fertilization. Eggs were placed in agar wells with their animal poles downward so that fertilization occurred preferentially in the equatorial plane, and confocal microscopy was used to provide a two-di...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(98)77650-7

    authors: Fontanilla RA,Nuccitelli R

    更新日期:1998-10-01 00:00:00

  • Binding of anionic lipids to at least three nonannular sites on the potassium channel KcsA is required for channel opening.

    abstract::In addition to the annular or boundary lipids that surround the transmembrane surface of the potassium channel KcsA from Streptomyces lividans, x-ray crystallographic studies have detected one anionic lipid molecule bound at each protein-protein interface in the homotetrameric structure, at sites referred to as nonann...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.107.117507

    authors: Marius P,Zagnoni M,Sandison ME,East JM,Morgan H,Lee AG

    更新日期:2008-03-01 00:00:00

  • Extension of a three-helix bundle domain of myosin VI and key role of calmodulins.

    abstract::The molecular motor protein myosin VI moves toward the minus-end of actin filaments with a step size of 30-36 nm. Such large step size either drastically limits the degree of complex formation between dimer subunits to leave enough length for the lever arms, or requires an extension of the lever arms' crystallographic...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2011.05.010

    authors: Liu Y,Hsin J,Kim H,Selvin PR,Schulten K

    更新日期:2011-06-22 00:00:00

  • Torque generation mechanism of F1-ATPase upon NTP binding.

    abstract::Molecular machines fueled by NTP play pivotal roles in a wide range of cellular activities. One common feature among NTP-driven molecular machines is that NTP binding is a major force-generating step among the elementary reaction steps comprising NTP hydrolysis. To understand the mechanism in detail,in this study, we ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2014.05.016

    authors: Arai HC,Yukawa A,Iwatate RJ,Kamiya M,Watanabe R,Urano Y,Noji H

    更新日期:2014-07-01 00:00:00

  • Light adaptation in turtle cones. Testing and analysis of a model for phototransduction.

    abstract::Light adaptation in cones was characterized by measuring the changes in temporal frequency responses to sinusoidal modulation of light around various mean levels spanning a range of four log units. We have shown previously that some aspects of cone adaptation behavior can be accounted for by a biochemical kinetic mode...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(91)82045-8

    authors: Tranchina D,Sneyd J,Cadenas ID

    更新日期:1991-07-01 00:00:00

  • On phasing the small-angle x-ray diffraction pattern from nerve myelin.

    abstract::Using a method they developed, Stamatoff and Krimm (1976) have phased swelling data from nerve myelin. Although most phases agree with those I determined previously, there are a few differences. In this letter the two different phasings, theirs and my own, are used to compute the corresponding electron-density profile...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(79)85242-X

    authors: Blaurock AE

    更新日期:1979-04-01 00:00:00

  • On the long-wavelength component of the light-harvesting complex of some photosynthetic bacteria.

    abstract::The effect of the presence of a minor antenna component in light-harvesting complexes of photosynthetic bacteria is investigated with numerical simulation employing the transition probability matrix method. A model antenna system of hexagonal symmetry is adopted, using as a working hypothesis that the minor component ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(92)81689-2

    authors: Fischer MR,Hoff AJ

    更新日期:1992-10-01 00:00:00

  • Pulsed electron spin resonance resolves the coordination site of Cu²(+) ions in α1-glycine receptor.

    abstract::Herein, we identify the coordination environment of Cu²(+) in the human α1-glycine receptor (GlyR). GlyRs are members of the pentameric ligand-gated ion channel superfamily (pLGIC) that mediate fast signaling at synapses. Metal ions like Zn²(+) and Cu²(+) significantly modulate the activity of pLGICs, and metal ion co...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2010.08.050

    authors: Ruthstein S,Stone KM,Cunningham TF,Ji M,Cascio M,Saxena S

    更新日期:2010-10-20 00:00:00

  • Diffusion of molecules on biological membranes of nonplanar form. A theoretical study.

    abstract::Lateral mobility of molecules on cell membranes has been recently studied by fluorescence photobleaching recovery (FPR) techniques. The interpretation of these results in terms of diffusion along the membranes is based on the assumption that the surface is planar, although biological membranes may have blebs and micro...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(82)84560-8

    authors: Aizenbud BM,Gershon ND

    更新日期:1982-06-01 00:00:00

  • Effect of noise on DNA sequencing via transverse electronic transport.

    abstract::Previous theoretical studies have shown that measuring the transverse current across DNA strands while they translocate through a nanopore or channel may provide a statistically distinguishable signature of the DNA bases, and may thus allow for rapid DNA sequencing. However, fluctuations of the environment, such as io...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2009.06.055

    authors: Krems M,Zwolak M,Pershin YV,Di Ventra M

    更新日期:2009-10-07 00:00:00

  • Analysis of phosphatidylinositol-4,5-bisphosphate signaling in cerebellar Purkinje spines.

    abstract::A 3D model was developed and used to explore dynamics of phosphatidylinositol-4,5-bisphosphate (PIP2) signaling in cerebellar Purkinje neurons. Long-term depression in Purkinje neurons depends on coincidence detection of climbing fiber stimulus evoking extracellular calcium flux into the cell and parallel fiber stimul...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.108.130195

    authors: Brown SA,Morgan F,Watras J,Loew LM

    更新日期:2008-08-01 00:00:00

  • A mesoscale model of DNA and its renaturation.

    abstract::A mesoscale model of DNA is presented (3SPN.1), extending the scheme previously developed by our group. Each nucleotide is mapped onto three interaction sites. Solvent is accounted for implicitly through a medium-effective dielectric constant and electrostatic interactions are treated at the level of Debye-Hückel theo...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2008.09.061

    authors: Sambriski EJ,Schwartz DC,de Pablo JJ

    更新日期:2009-03-04 00:00:00

  • Differential effects of amino-terminal distal and proximal domains in the regulation of human erg K(+) channel gating.

    abstract::The participation of amino-terminal domains in human ether-a-go-go (eag)-related gene (HERG) K(+) channel gating was studied using deleted channel variants expressed in Xenopus oocytes. Selective deletion of the HERG-specific sequence (HERG Delta138-373) located between the conserved initial amino terminus (the eag or...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(00)76286-2

    authors: Viloria CG,Barros F,Giráldez T,Gómez-Varela D,de la Peña P

    更新日期:2000-07-01 00:00:00

  • How cells tune viral mechanics--insights from biophysical measurements of influenza virus.

    abstract::During replication, the physical state of a virus is controlled by assembly and disassembly processes, when particles are put together and dismantled by cellular cues, respectively. A fundamental question has been how a cell can assemble an infectious virus, and dismantle a virus entering an uninfected cell and thereb...

    journal_title:Biophysical journal

    pub_type: 杂志文章,评审

    doi:10.1016/j.bpj.2014.04.025

    authors: Greber UF

    更新日期:2014-06-03 00:00:00

  • Protein-induced membrane curvature investigated through molecular dynamics flexible fitting.

    abstract::In the photosynthetic purple bacterium Rhodobacter (Rba.) sphaeroides, light is absorbed by membrane-bound light-harvesting (LH) proteins LH1 and LH2. LH1 directly surrounds the reaction center (RC) and, together with PufX, forms a dimeric (RC-LH1-PufX)2 protein complex. In LH2-deficient Rba. sphaeroides mutants, RC-L...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2009.04.031

    authors: Hsin J,Gumbart J,Trabuco LG,Villa E,Qian P,Hunter CN,Schulten K

    更新日期:2009-07-08 00:00:00

  • Influence of the environment and probes on rapid DNA sequencing via transverse electronic transport.

    abstract::We study theoretically the feasibility of using transverse electronic transport within a nanopore for rapid DNA sequencing. Specifically, we examine the effects of the environment and detection probes on the distinguishability of the DNA bases. We find that the intrinsic measurement bandwidth of the electrodes helps t...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.106.102269

    authors: Lagerqvist J,Zwolak M,Di Ventra M

    更新日期:2007-10-01 00:00:00

  • Mechanosensitive Junction Remodeling Promotes Robust Epithelial Morphogenesis.

    abstract::Morphogenesis of epithelial tissues requires tight spatiotemporal coordination of cell shape changes. In vivo, many tissue-scale shape changes are driven by pulsatile contractions of intercellular junctions, which are rectified to produce irreversible deformations. The functional role of this pulsatory ratchet and its...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2019.09.027

    authors: Staddon MF,Cavanaugh KE,Munro EM,Gardel ML,Banerjee S

    更新日期:2019-11-05 00:00:00

  • Single-cell adhesion tests against functionalized microspheres arrayed on AFM cantilevers confirm heterophilic E- and N-cadherin binding.

    abstract::We assess the cross-reactivity of both cellular as well as recombinant E- and N-cadherins using functionalized bead arrays assembled on atomic-force-microscope cantilevers. This new approach builds upon and enhances the utility of a recently developed force probe that integrates a custom-built, horizontal atomic force...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2010.11.013

    authors: Ounkomol C,Yamada S,Heinrich V

    更新日期:2010-12-15 00:00:00

  • In situ mechanical analysis of myofibrillar perturbation and aging on soft, bilayered Drosophila myocardium.

    abstract::Drosophila melanogaster is a genetically malleable organism with a short life span, making it a tractable system in which to study mechanical effects of genetic perturbation and aging on tissues, e.g., impaired heart function. However, Drosophila heart-tube studies can be hampered by its bilayered structure: a ventral...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2011.10.042

    authors: Kaushik G,Fuhrmann A,Cammarato A,Engler AJ

    更新日期:2011-12-07 00:00:00

  • Open-Boundary Molecular Dynamics of a DNA Molecule in a Hybrid Explicit/Implicit Salt Solution.

    abstract::The composition and electrolyte concentration of the aqueous bathing environment have important consequences for many biological processes and can profoundly affect the behavior of biomolecules. Nevertheless, because of computational limitations, many molecular simulations of biophysical systems can be performed only ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2018.02.042

    authors: Zavadlav J,Sablić J,Podgornik R,Praprotnik M

    更新日期:2018-05-22 00:00:00

  • Viscoelastic properties of living embryonic tissues: a quantitative study.

    abstract::A number of properties of certain living embryonic tissues can be explained by considering them as liquids. Tissue fragments left in a shaker bath round up to form spherical aggregates, as do liquid drops. When cells comprising two distinct embryonic tissues are mixed, typically a nucleation-like process takes place, ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(98)77932-9

    authors: Forgacs G,Foty RA,Shafrir Y,Steinberg MS

    更新日期:1998-05-01 00:00:00

  • Learning the Formation Mechanism of Domain-Level Chromatin States with Epigenomics Data.

    abstract::Epigenetic modifications can extend over long genomic regions to form domain-level chromatin states that play critical roles in gene regulation. The molecular mechanism for the establishment and maintenance of these states is not fully understood and remains challenging to study with existing experimental techniques. ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2019.04.006

    authors: Xie WJ,Zhang B

    更新日期:2019-05-21 00:00:00

  • Structural and functional features of one- and two-headed biotinated kinesin derivatives.

    abstract::The oligomeric structure was determined for four recombinant kinesin derivatives containing N-terminal fragments of the kinesin alpha-subunit. Some of the proteins were dimeric (two-headed) molecules with mechanochemical properties similar to those of intact kinesin. Comparison of the primary and quaternary structures...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:

    authors: Gelles J,Berliner E,Young EC,Mahtani HK,Perez-Ramirez B,Anderson K

    更新日期:1995-04-01 00:00:00