Dissection of open chromatin domain formation by site-specific recombination in Drosophila
JOURNAL OF CELL SCIENCE
Authors: Zielke, Thomas; Saumweber, Harald
Abstract
Drosophila polytene interphase chromosomes provide an ideal test system to study the rules that define the structure of chromatin domains. We established a transgenic condensed chromatin domain cassette for the insertion of large pieces of DNA by site-specific recombination. Insertion of this cassette into open chromatin generated a condensed domain, visible as an extra band on polytene chromosomes. Site-specific recombination of DNA sequence variants into this ectopic band allowed us to compare their capacity for open chromatin formation by cytogenetic methods. We demonstrate that the 61C7-8 interband DNA maintains its open chromatin conformation and epigenetic state at an ectopic position. By deletion analysis, we mapped the sequences essential for open chromatin formation to a 490-bp fragment in the proximal part of the 17-kb interband sequence. This fragment overlaps binding sites for the chromatin protein Chriz (also known as Chro), the histone kinase Jil-1 and the boundary element protein CP190. It also overlaps a promoter region that locates between the Rev1 and Med30 transcription units.
Detection of susceptibility loci on APOA5 and COLEC12 associated with metabolic syndrome using a genome-wide association study in a Taiwanese population
ONCOTARGET
Authors: Lin, Eugene; Kuo, Po-Hsiu; Liu, Yu-Li; Yang, Albert C.; Tsai, Shih-Jen
Abstract
Background: Although the association of single nucleotide polymorphisms (SNPs) with metabolic syndrome (MetS) has been reported in various populations in several genome-wide association studies (GWAS), the data is not conclusive. In this GWAS study, we assessed whether SNPs are associated with MetS and its individual components independently and/or through complex interactions in a Taiwanese population. Methods: A total of 10,300 Taiwanese subjects were assessed in this study. Metabolic traits such as waist circumference, triglyceride, high-density lipoprotein (HDL) cholesterol, systolic and diastolic blood pressure, and fasting glucose were measured. Results: Our data showed an association of MetS at the genome-wide significance level (P < 8.6 x 10(-8)) with two SNPs, including the rs662799 SNP in the apolipoprotein A5 (APOA5) gene and the rs16944558 SNP in the collectin subfamily member 12 (COLEC12) gene. Moreover, we identified the effect of APOA5 rs662799 on triglyceride and HDL, the effect of rs1106475 in the actin filament associated protein 1 like 2 (AFAP1L2) gene on systolic blood pressure, and the effect of rs17667932 in the mediator complex subunit 30 (MED30) gene on fasting glucose. Additionally, we found that an interaction between the APOA5 rs662799 and COLEC12 rs16944558 SNPs influenced MetS, high triglyceride, and low HDL. Conclusions: Our study indicates that the APOA5 and COLEC12 genes may contribute to the risk of MetS and its individual components independently as well as through gene-gene interactions.