1Q12 Loci Movement in the Interphase Nucleus Under the Action of ROS Is an Important Component of the Mechanism That Determines Copy Number Variation of Satellite III (1q12) in Health and Schizophrenia

Abstract

Introduction: Genome repeat cluster sizes can affect the chromatin spatial configuration and function. Low-dose ionizing radiation (IR) induces an adaptive response (AR) in human cells. AR includes the change in chromatin spatial configuration that is necessary to change the expression profile of the genome in response to stress. The 1q12 heterochromatin loci movement from the periphery to the center of the nucleus is a marker of the chromatin configuration change. We hypothesized that a large 1q12 domain could affect chromatin movement, thereby inhibiting the AR. Materials and Methods: 2D fluorescent in situ hybridization (FISH) method was used for the satellite III fragment from the 1q12 region (f-SatIII) localization analysis in the interphase nuclei of healthy control (HC) lymphocytes, schizophrenia (SZ) patients, and in cultured mesenchymal stem cells (MSCs). The localization of the nucleolus was analyzed by the nucleolus Ag staining. The non-radioactive quantitative hybridization (NQH) technique was used for the f-SatIII fragment content in DNA analysis. Satellite III fragments transcription was analyzed by reverse transcriptase quantitative PCR (RT-qPCR). Results: Low-dose IR induces the small-area 1q12 domains movement from the periphery to the central regions of the nucleus in HC lymphocytes and MSCs. Simultaneously, nucleolus moves from the nucleus center toward the nuclear envelope. The nucleolus in that period increases. The distance between the 1q12 domain and the nucleolus in irradiated cells is significantly reduced. The large-area 1q12 domains do not move in response to stress. During prolonged cultivation, the irradiated cells with a large

The Role of Human Satellite III (1q12) Copy Number Variation in the Adaptive Response during Aging, Stress, and Pathology: A Pendulum Model

“…In response to stress, 1q12 loci move from the perimembrane region (r > 0.75) deep into the nucleus and converge with each other. A similar 1q12 loci movement was also observed when a proliferative stimulus PHA had been applied [133]. Surprisingly, the stress-induced 1q12 loci movement depended on the locus size.…”

“…This hypothesis was verified in studies of the response of human cultured lymphocytes and mesenchymal stem cells (MSC) to low doses of IR, PHA stimulation and hydrogen peroxide. The response to the stress and proliferative stimuli associated with the 1q12 loci movement toward the nucleus center was not realized in the cells with a too large 1q12 loci size [133].…”

“…The 1q12 heterochromatin loci movement from the periphery to the center of the nucleus is a marker of the chromatin configuration change. It was hypothesized that a large 1q12 domain could affect chromatin movement, thereby hindering the translocation and inhibiting the adaptive response (AR) [133].…”

Mesenchymal Stem Cells Early Response to Low-Dose Ionizing Radiation

“…Two variants of cell staining were used: PI staining of the nuclei ( Figure 5C1 ) and polymer F-actin staining ( Figure 5C2 ). In MSCs, PI allowed localizing the nucleoli ( Konkova et al, 2020 ). The F-actin reagent allowed tracing the stress fibers formation in response to ROS after LDIR ( Ermakov et al, 2011 ).…”

Копийность Рибосомных Генов При Шизофрении

“…Практически все авторы рассматривают только уникальные или малокопийные гены. Мы впервые обратили внимание на многокопийные гены, кодирующие рРНК рибосом (рДНК), у больных шизофренией [3][4][5].…”