HydrophobicVarietyofChromatininCellularprocesses.doc

精品論文hydrophobic variety of chromatin in cellular processeswang xiaoencollege of biology and chemical engineering weifang college of education college of weifangeducation qingzhou city, shandong province (262500)e-mail: 330518204abstractthe discrepancies of molecular structure between dna and rna result to their different nature.deoxyribose constituting dna is more hydrophobic than ribose constituting rna. on the chemical principle of similar substances can be soluble with each other (ssseo), here, i propose that the dna, nucleoplasm, and decondensational state of chromatin are more hydrophobic than the rna, cytoplasm, and condensational state, respectively. based on this point, many biological processes, such as the disappearance and reappearance of nuclear envelope during division of eucaryote, the spontaneous exit of rna to cytoplasm after synthesis within nucleus, and the relation between chemical modifications of chromatin and some important cellular processes, may be well explicated.keywords: hydrophobic variety of chromatin; disappearance and reappearance of nuclear envelop;deoxyribose; ribose1. introductionin biology the dna and rna are perhaps the most widely studied macromolecules, yet their properties in living cells are still not well understood, because intra-nuclear composition of eucaryotic cells is very complex. only number of endogenous nucleolar proteins characterized by andersen and his co-workers is flabbergasted as much as 489 1. although the structure of the nucleosome core, which is the substrate for dna replication, recombination, transcription andrepair, has nearly been resolved at near-atomic level, it is controversial to the fundamental information about the organization of nucleosomes in the fibre 2. understanding the structural and molecular basis of mitotic chromosomal condensation and decondensation remains also a basic challenge in cell biology. to date, three models relating with mitotic chromosome structure (radial loop, hierarchical folding, and network models) have been proposed 3, but no any single model can fit the preponderance of experiment data, with only contradictory evidence supporting one or another model 4. however, it has been noted that solvent molecules, water, play an important role in promoting histonedna association by providing further stability to direct proteindna interactions, and in formation of many additional interactions between more distantly related elements 5. moreover, growing awareness of the remarkable diversity, unintelligible complexity, and biological specificity of the interactions between dna and histone, between two histones, between histone and non-histone protein, and between dna and non-histone protein 6, 7, 8, 9, 10 had also caused me to favour a completely different view that the change in hydrophobic property of chromatin surface may play a pivotal role in linkage between its structure and biological function11. by this view, here, we re-investigate several based questions in biology by analyzing the hydrophobic disparity between rna and dna, between nucleoplasm and cytoplasm, and between different condensed states of chromatin.2.dna molecules are more hydrophobic than rnaboth dna and rna molecules are the linear polymers constituted by nucleotide monomers using phosphodiester bonds. each nucleotide monomer made of three parts: phosphate, sugar, and base. only constitutionally discrepancy between dna and rna molecules is different nucleoside-residues (sugar and base residues).- 6 -2.1 disparity in sugarsit is well known that the sugar of constituting rna is-d-ribose and of dna is -d-deoxyribose in which hydroxyl group (-oh) on c atom 2 in ribose is substituted by a hydrogen atom (-h). this hydroxyl group is an only one of strong polar groups (strong hydrophilic groups) in ribose within rna molecule because all other three (on c1, c3, and c5) of hydroxyl groups have been used to form covalent bonding. apparently, hydrophobic property of deoxyribose is stronger than ribose because the carbon-hydroxyl group (c-oh) is hydrophilicwhereas the carbon-hydrogen group (c-h) is hydrophobic (fig. 1).5hoch2 ooh1oh43c5n hrnarna4c32h612nooh ohohh5odnahoch24ooh1chch3ch3c435n h612dnah32no ohhfigure 1. -d-ribose (upper) and-d- deoxyribose (bottom)constituting rna and dna, respectively. hydrophobic property of dna is stronger than rna because the c-oh on c2 is hydrophilic group whereas the c-h is hydrophobic group.figure 2. hydrophobic comparison between uracil (upper), constitutes rna, and thymine (bottom), constitutes dna. hydrophobic property of the methyl group is little stronger than the hydrogen atom on c atom5 in pyrimidine cycle.such a substitution, deoxidation of hydroxyl group linking c2, is perhaps important for formatting double strands of dna molecules, binding dna with histone octamer two copies each of histones h2a, h2b, h3, and h44, associating linker dna to histone h1 or h5, and all functions about dna replication and transcription.2.2 disparity in basesit is well also known that four bases of constituting rna are adenine (a), guanine (g), cytosine (c), and uracil (u), generally, and that of dna are adenine(a), guanine (g), cytosine (c), and thymine (t). in composition both rna and dna contain adenine(a), guanine (g), and cytosine (c). only difference between rna and dna is that rna molecule contains uracil but dna contains thymine. thymine is compound that h atom on c atom 5 in uracil cycle is substituted by methyl group (fig. 2). chemically, electronegativity of carbon atoms with differenthybrid state is in the order 11sp sp2 sp3.since the c atom 5 in pyrimidine cycle adopts sp2 hybridization and c atom in methyl group adopts sp3 hybridization, polarity of the c-h bond on site 5 in pyrimidine cycle is slightly larger than c-h bond in methyl group. hence, hydrophobic property of thymine is a little stronger than uracil. taken together, our theoretical analysis suggests that hydrophobic property of dna isstronger than rna. in other words, rna molecule is more hydrophilic than dna.3 intra-nuclear environment is more hydrophobic than cytoplasm.a32 102ch (ch )ch coona+booch2op=och3(ch2)16-c-o-cho+ch3(ch2)14-c-o-ch2ch2ch2nh3ofigure3. a) sodium dodecyl benzene sulfonate with a hydrophobic tail, which is major effective ingredient of many detergents and is an amphipathic molecule. b) molecular structure of a sort of cephalins containing two fatty acid tails. these two tails are hydrophobic alkylresidue-waterwateroilwater+ -+- +cytoplasmic sidenucleoplasmic side+ -+ - +water+ -+ -+ - +protein+ -figure 4. schematic of vesicle in oil in water formed by the surfactant molecules such as soap or detergent. the vesicle membrane lowers free energy of interface between water and oil. there is a very large interfacial energy between two sides of vesicle membrane.figure 5. schematic of nuclear membrane formed by protein and bilayer of phospholipid molecules such as lecithin and cephalin. such a nuclear membrane can properly reduce interfacial free energy between cytoplasm and nucleoplasm, despite the littler interfacial energy than between water andoil.to the eucaryote, generally, dna is located in nucleus, whereas the bulk of rna after synthesis intra-nucleus will be extruded to cytoplasm. based on the chemical principle of ssseo, polar solutes dissolve easily in polar solvents, and non-polar solutes dissolve easily in non-polar solvents. it appears to we that cytoplasm is more hydrophilic than intra-nucleus. emulsifyingphenomenon is a well instance cited to explain the interaction of affinity with solubility between solute and solvent 12. the major effective ingredient of both soap and detergent is a sort of surface-active agents so called amphipathic molecule. generally, surfactant molecule contains both a polar group lyotropic, such as carboxyl, amino, and hydroxyl group, and a non-polar group indissoluble, such as alkyl group (fig.3).when a small amount of hydrophobic liquid (such as oils) is added to an aqueous solution containing soap or detergent the surfactant molecules form vesicle-like liquid membranes between hydrophobic liquid droplets and the solution after stirring, and pack these droplets into solution in oil in water (fig.4). since existence of the liquid membrane constituted by surfactant molecules decreases in interfacial energy and lowers the free energy of the whole of system. hence, this is a spontaneous process. because dna molecules contain more hydrophobic groups than rna a bulk of colloidal solution showing less hydrophilic than cytoplasm, the nucleoplasm, appears when double strands of dna molecules combine with certain proteins by hydrophilic bonds major to form some linear complexes showing more hydrophobic property than before combination, and when aggregate together dispersively. resembling membrane of soap bubbles the nuclear membrane of cell is also composed of amphipathic molecules such as lecithin and cephalin (fig.5). therefore, the existence of nuclear membrane can certainly lower the interfacial energy between nucleus and cytoplasm. however, the nuclear envelope must be bilayer lipid membrane, for hydrophilic property of nucleoplasm is less than cytoplasm but its hydrophobic property is also far less than oils. in other words, the interfacial energy between the two phases is smaller than between oil and water. apparently, since so small interfacial energy, a monolayer of amphipathic molecules is not proper. thus, nuclear envelope is regulated by both sort and number of amphipathic (lipid) molecules within each layer of the bilayer lipid membrane to fit the interfacial energy between nucleus and cytoplasm, resulting in a lowest free energy of the whole of system.based on both the chemical principle of ssseo and the layer of amphipathic molecule lowering interfacial free energy, it perhaps is of assist to understand some phenomena of molecular cell biology such as the disappearance and reappearance of nuclear envelope during division of eucaryote, the spontaneous exit of rna synthesized within nucleus to cytoplasm, the no nucleus envelope for prokaryote containing less of dna molecules, and the relation betweengenomic hypomethylation and tumorigenesis 13.4. nucleolar hydrophobic property is between nucleoplasm and cytoplasm possiblyby analysis above, we speculate that hydrophobic property of nucleolus may be between nucleoplasm and cytoplasm, because (1) a lot of rnas, as which are more hydrophilic than dna, are synthesized in nucleolus14, (2) nucleolar and cytoplasmic rna had similar base compositions, whereas nucleoplasmic rna was distinct15. when transcription the chromatin decondensates and unfolds, whereas hydrophilic property of dna molecule strengthens because broken and exposing of hydrogen bonds formed by bases between two strands of dna. similarly, we can speculate thatrna polymerases is more hydrophilic than dna polymerases. after synthesis and processing, the overwhelming majority of rnas will be excreted into cytoplasm from intra-nucleus. recent years, dynamics of rnas has received the lions share of interest1. for the intra-nuclear movement and extrication of individual messenger rna (mrna) in living mammalian cells, it has widely been investigated and has found at least four conclusions: (a) the mobility of mrna was dominant bysimple diffusion; (b) some single mrna-protein complexes (mrnps) were partially aggregated in the nonhomogenous nuclear environment, whereas no accumulation at subnuclear domains; (c)this motion of mrnps was energy-independent notwithstanding the highly atp-dependent nuclear environment; and (d) the mrna was limited to move only in chromatin-poor domains and repelled by newly formed chromatins. accordingly, it is possible that cellular metabolism affects the diffusion of rna and forms a hydrophilic gradient along their way from the transcription site to cytoplasm via nuclear pore. this hydrophilic gradient is perhaps driving force for rna moving and excreting.5. the condensed state of chromatin is more hydrophilic than unfolding state.although, analysis of the relationship between cellular process and the condensed states of chromatin and change in large-scale chromatin structure7, 16, 17, 18 has focused largely on lower levels of chromatin structure, such as targeting of many activators, acetylation, phosphorylation and methylation of histone tails, and recruitment of some enzymes7, 19, 20, the molecular mechanism of these changes as well as the biological significance are very complex questions that no solution well now. based on following experiment facts 4 and on structural difference between dna and rna, here, it is, first, proposed that change in folding state of dna molecules varies in company with hydrophilic property of chromosome surfaces. in low-ionic-strength (low polarization) solution, a full extended “beads-on-a-string” fibers of chromatin may be extracted. when enhance the ionic strength of solution or add 1 to 2 mm divalent cation a heterogeneous population of folded arrays, as a compact 30-nm fiber of chromatin, can be obtained. in larger-cation concentration (higher polarization), higher-order condensed chromatin structure (30 nm in diameter) can be segregated.in the early and middle prophase of mitosis the dna molecules associate with histone and/or chromatin-associated proteins, condense, and fold stepwise. in this process, on the one hand, dna molecules consume more hydrophobic bonds and less hydrophilic bonds whereas more hydrophilic groups are exposed to out surfaces of the condensing structures. on the other hand, the specific surface area of chromatin is reduced rapidly. together, factors of the two hands lower the hydrophobic effect of nucleoplasm whereas enhance their hydrophilic property. when hydrophilic property of the chromosomal surfaces is close to of cytoplasm in the late prophase the free energy of the system might go up if the nuclear envelope existed still. consequently, the nuclear envelope disrupts spontaneously and disappears gradually.when cell enters telophase, just the opposite, the condensed chromosomes within each newborn daughter cell start to unfold, and decondense, and disperse diffusely. a large number of hydrophobic bonds used in condensed structure have been broken into hydrophobic groups, which are exposed to solution. when dna molecules of whole cell unfold in maximum extent and agglutinate diffusely into a mass of colloid in which hydrophobic property is larger than in cytoplasm, the interfacial free energy between the dna colloid and cytoplasm must enhance. to lower the free energy of system, some amphipathic lipid molecules come automatically on the interface, and this spontaneous process makes new nuclear envelope to form voluntarily.6. final instructionsin summary, to understand how eukaryotic genomes are manipulated within a chromatin environment, we have to consider the change in hydrophobic property of chromatin. all of a diverse array of post-translational modifications for hostones and dna methylation must lead to variations in hydrophobic property or radical polarity of their self. for example, the methylation can make hydrophilic group to hydrophobic, whereas the phosphorylation of a hydroxyl or aminogroup can make positive group into negative. these issues are vital for gaining a deeper understanding of nature of dna and rna in live cells, such as replication, transcription, and translation of genes, because change in hydrophilic or electropolar property for those groups on some key sites relates directly with association between dna and histone, between two histones, between histone and non-histone protein, between dna and non-histone protein, between dna and rna, and between rna and proteins.references1 andersen, j. s., lam, y. w., leung, a. k. l., ong, s. e., lyon, c. e., lamond, a. i., and mann, m. nucleolar proteome dynamics. nature. 433 (7021): 77-83 (2005).2 schalch, t., duda, s., sargent, d. f., and richmond, t. j. x-ray structure of a tetranucleosome and its implications for the chromatin fibre. nature. 436 (7047): 138-141 (2005).3 kireeva, n., lakonishok, m., kireev, i., hirano, t., and belmont, a. s. visualization of early chromosome condensation : a hierarchical folding, axial glue model of chromosome structure. journal of cell biology, 166 (6):775-785 (2004).4 horn, p. j., and peterson, c. l. chromatin higher order folding: wrapping up transcription. science. 297 (5588): 18241827 (2002).5 davey, c. a., sargent, d. f., luger, k., maeder, a. w., and richmond, t. j. solvent mediated interactions in the structure of the nucleosome core particle at 1.9 resolution. journal of molecular biology. 319 (5):1097-1113 (2002).6 danzer, j. r. and wallrath, l. l. mechanisms of hp1-mediated gene silencing in drosophila. development.131 (15): 3571-3580 (2004).7 verschure, p. j.; van der kraan, i.; de leeuw, w.; van der vlag, j.; carpenter, a. e.; belmont, a. s., and vandriel, r.in vivo hp1 targeting causes large-scale chromatin conde