Spatial and temporal organization of the genome: Current state and future aims of the 4D nucleome project

The four-dimensional nucleome (4DN) consortium studies the architecture of the genome and the nucleus in space and time. We summarize progress by the consortium and highlight the development of technologies for (1) mapping genome folding and identifying roles of nuclear components and bodies, proteins, and RNA, (2) characterizing nuclear organization with time or single-cell resolution, and (3) imaging of nuclear organization. With these tools, the consortium has provided over 2,000 public datasets. Integrative computational models based on these data are starting to reveal connections between genome structure and function. We then present a forward-looking perspective and outline current aims to (1) delineate dynamics of nuclear architecture at different timescales, from minutes to weeks as cells differentiate, in populations and in single cells, (2) characterize cis-determinants and trans-modulators of genome organization, (3) test functional consequences of changes in cis- and trans-regulators, and (4) develop predictive models of genome structure and function

Spatial and Temporal Organization of the Genome: Current State and Future Aims of the 4D Nucleome Project

The four-dimensional nucleome (4DN) consortium studies the architecture of the genome and the nucleus in space and time. We summarize progress by the consortium and highlight the development of technologies for (1) mapping genome folding and identifying roles of nuclear components and bodies, proteins, and RNA, (2) characterizing nuclear organization with time or single-cell resolution, and (3) imaging of nuclear organization. With these tools, the consortium has provided over 2,000 public datasets. Integrative computational models based on these data are starting to reveal connections between genome structure and function. We then present a forward-looking perspective and outline current aims to (1) delineate dynamics of nuclear architecture at different timescales, from minutes to weeks as cells differentiate, in populations and in single cells, (2) characterize cis-determinants and trans-modulators of genome organization, (3) test functional consequences of changes in cis- and trans-regulators, and (4) develop predictive models of genome structure and function

Orderly assembly underpinning built-in asymmetry in the yeast centrosome duplication cycle requires cyclin-dependent kinase

Funder: CSC Cambridge International ScholarshipAsymmetric astral microtubule organization drives the polarized orientation of the S. cerevisiae mitotic spindle and primes the invariant inheritance of the old spindle pole body (SPB, the yeast centrosome) by the bud. This model has anticipated analogous centrosome asymmetries featured in self-renewing stem cell divisions. We previously implicated Spc72, the cytoplasmic receptor for the gamma-tubulin nucleation complex, as the most upstream determinant linking SPB age, functional asymmetry and fate. Here we used structured illumination microscopy and biochemical analysis to explore the asymmetric landscape of nucleation sites inherently built into the spindle pathway and under the control of cyclin-dependent kinase (CDK). We show that CDK enforces Spc72 asymmetric docking by phosphorylating Nud1/centriolin. Furthermore, CDK-imposed order in the construction of the new SPB promotes the correct balance of nucleation sites between the nuclear and cytoplasmic faces of the SPB. Together these contributions by CDK inherently link correct SPB morphogenesis, age and fate

Türk Toplumunda Apolipoprotein B Geni Ecorı Polimorfizminin Aterosklerotik Hastalarda ve Sağlıklı Kişilerde Araştırılması

Apolipoprotein B (Apo B) lipid metabolizmasında önemli rol oynamaktadır ve Apo B geninin varyasyonları aterosklerozun gelişimini etkilemektedir. Apo B geni polimorfiktir ve EcoRI kesim yeri kodlama bölgesi içinde bulunur. Çalışmamızın amacı Apo B geni EcoRI polimorfizminin Türk toplumunda ateroskleroz gelişiminde risk faktörü olup olmadığının araştırılması ve lipid parametreleri üzerindeki mevcut etkilerinin saptanmasıdır. Çalışma tedavi görmekte olan 64 aterosklerozlu (48 erkek ve 16 kadın) ve 45 kontrol (1 1 erkek ve 34 kadın) örnek üzerinde yapıldı. Apo B geni EcoRI polimorfizmi, izole edilen DNA örneklerinden polimeraz zincir reaksiyonu ve EcoRI restriksyon izotiplemesi ile tespit edildi. Genotip frekansları EcoRI kesim bölgesi varlığı için homozigot (+/+), EcoRI kesim bölgesi yokluğu için homozigot (-/-), ve heterozigotlar (+/-) için sırasıyla aterosklerotik grupta %73.4, %0, ve %26.6; kontrol grup için ise %75.3, %2.2, %22.2 olarak saptandı. Trigliserid, ve glikoz düzeylerinin ateroskleroz grubunda kontrol grubuna göre anlamlı oranda yüksek olduğu saptandı (p<0.001). Apo B geni EcoRI polimorfizminin LDL-kolesterol seviyesini sınırda anlamlı oranda etkilediği bulundu (p=0.074).Apolipoprotein B (Apo B) gene plays a central role in lipid metabolism, and genetic variations in this gene contribute to atherosclerosis development. Apo B gene is a highly polymorphic gene, and EcoRI cutting site is located in the coding region. The aim of the study was to investigate the relationship between Apo B gene EcoRI polymorphism and lipid parameters in atherosclerotic and healthy subjects from Turkish population and to evaluate the EcoRI genotype frequencies in these groups. The study was performed on 64 atherosclerotic (48 male and 1 6 female) and 45 control (1 1 male and 34 female) subjects. DNA has been isolated from peripheral blood samples, and part of interest from Apo B gene has been amplified by PCR. The genotype frequencies for the presence of EcoRI restriction site (+/+), absence of EcoRI restriction site (-/-), and heterozygotes (-/+) were found as 73.4%, 0%, and 26.6% for the atherosclerotic group; and 75.3%, 2.2%, 22.2% for the control group, respectively. Triglyceride and glucose levels have been found significantly increased in atherosclerotic group in comparison with controls (p<0.001). Apo B gene EcoRI polymorphism was found to effect LDL-cholesterol concentrations at a borderline significant level (p=0.074)