| Summary: | Abstract Background Even as the eukaryotic stranded DNA is known to heterochromatinize at the nuclear envelope in response to mechanical strain, the precise mechanistic basis for alterations in chromatin gene transcription in differentiating cell lineages has been difficult to determine due to limited spatial resolution for detection of shifts in reference to a specific gene in vitro. In this study, heterochromatin shift during euchromatin gene transcription has been studied by parallel determinations of DNA strand loop segmentation tropy nano-compliance (esebssiwaagoT Q units, linear nl), gene positioning angulation in linear normal two-dimensional (2-D) z, y-vertical plane (anglemetry, 0), horizontal alignment to the z, x-plane (vectormetry; m A, m M, a.u.), and by pressuromodulation mapping of differentiated neuron cell sub-class operating range for neuroaxis gene expression in reference to tissue macro-compliance (P eff). Methods The esebssiwaagoT Q effective pressure unit (P eff) maxima and minima for horizontal gene intergene base segment tropy loop alignment were determined (n = 224); the P eff esebssiwaagoT Q quotient were determined (n = 28) for analysis of gene intergene base loop segment tropy structure nano-compliance (n = 28; n = 188); and gene positioning anglemetry and vectormetry was performed (n = 42). The sebs intercept-to-sebssiwa intercept quotient for linear normalization was determined (b sebs/b sebssiwa) by exponential plotting of sub-episode block sum (sebs) (x 1, y 1; x 2, y 2) and sub-episode block sum split integrated weighted average (sebssiwa) functions was performed, and the sebs – sebssiwa function residuals were determined. The effective cell pressure (P eff)-to-angle conversion factor was determined, ϴ A = (1E + 02) {0.90 – [(0.000 + a ≥ x < 0.245) (1.208)] form was applied for anisotropic gene anglemetry, and the ϴ M = (1E + 02) {0.90 – [1.208 (0.245 ≥ x ≤ m)] form was applied for mesotropic gene anglemetry. Two-step Tukey range t-test was performed for inter-group comparisons of b sebs/b sebssiwa quotients and sebs – sebssiwa normalized residuals between tier 1 (P eff ≤ 0.200; n = 11) and tier 2 (P eff > 0.200 ≤ 0.300; n = 6), between tier 1 and tier 3 (P eff > 0.300; n = 8), and between tier 3 and tier 2 (α = 0.05). Results Based on the results of this study, I) heterochromatin strand DNA loop micro-segmentation structural nano-compliance is either amorphousity, anisotropy or mesotropy loop segment forms perceiving various grades of the asymmetric tropy viscosity effect, where between 3-to-5 and 8-to-11 genes are arranged as one or two in-tandem alternating anisotropic and mesotropic gene(s), or as in-tandem anisotropic or mesotropic genes in juxtaposition separated by intergene tropy base distance; for example, the anisotropy loop segment form between positions − 12 to + 15 in reference LMNA (P eff, 0.184; θ A = 68.40) on human 1q22 (+) is: 5′-0.234-(a− 12)-0.272 (m− 11)-0.229 (a− 10)-0.211 (a− 9)-0.269 (m− 8)-0.144 (a− 7)-0.314 (m− 6)-0.268 (m− 5)-0.176 (a− 4)-0.260 (m− 3)-0.259 (m− 2)-0.270 (m− 1)-0.184 (a0)-0.135 (m+ 1)-0.395 (m+ 2)-0.146 (a+ 3)-0.212 (a+ 4)-0.336 (m+ 5)-0.287 (m+ 6)-0.153 (a+ 7)-0.283 (m+ 8)-0.193 (a+ 9)-0.269 (m+ 10)-0.199 (a+ 11)-0.146 (a+ 12)-0.190 (a+ 13)-0.188 (a+ 14)-0.243 (a+ 15)-3′, which begins at the 5′ end with DAP3 (P eff 0.234); II) mesotropy loop form genes are positioned between 11.7 and 60.40 (CD34) in the z, y-vertical plane, whereas anisotropy loop form genes positioned between 60.5 and 82.30 (MIR4537) in the z, y-vertical plane; III) the relationship between effective pressure and momentum is inverse proportionality, P eff (0.064 ≥ x < 0.245) · m A = P eff (0.245 ≥ x ≤ 0.648) · m M; IV) the interval for peripheral lower motor neuron (lmn) gene expression is definable as being between a P eff of 0.434 and 0.311 (> 0.305), between a P eff of 0.305 and 0.213 for cerebrocortical upper motor neurons, between a P eff of 0.318 and 0.203 for hippocampocortical neurons, and between a P eff of 0.298 and 0.217 for basal ganglia spiny neurons; therefore, there exists an inverse relationship between effective range of whole cell compliance and tissue macro-compliance (R effective whole cell compliance ˑ T macro-compliance = k), in which case the range for mesenchymal cell (MSC) gene expression is delineable as being between a Peff of 0.648 and <= 0.118 esebssiwaagoTQ units; and V) RGS18 (P eff 0.205; θ M = 65.20), RGS16 (P eff 0.251; θ M = 59.70; human paralog of murine RGS4), lnc-RXFP4–5 (P eff , 0.314; θ M = 52.10; pituit), RGS13 (P eff ; 0.360, θ M = 46.50), CEACAM1 (P eff , 0.384; θ M = 43.60), SLC25A44 (P eff , 0.395; θ M = 42.30) and RGS21 (P eff , 0.413; θ M = 40.10) are expressed within the lower motor neuron (lmn)-upper motor neuron (umn) neural cell axis; and TSACC (P eff , 0.336; θ M = 49.40) and JUND (P eff , 0.344; θ M = 48.40) are non-cell specific developmental biomarkers. Conclusions Based on the findings of this study considered together, the precise mechanistic basis for alterations in chromatin gene transcription eukaryotic stranded heterochromatin arranged by structural pressurotopy nano-compliance in DNA stand loop segments is effective cell pressure (P eff ) regulated shifting of transcriptionally active DNA in-between the inner nuclear envelope margin and the peripheral nucleoplasm edge and the z, x-plane horizontal alignment of a gene by gene specific P eff within the cell specific effective range of whole cell compliance in reference to tissue macro-compliance. The findings of this study are therefore applicable to the further study of changes in gene transcription in response to applied mechanical strain-mediated alterations in nuclear envelope deformability in silico.
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