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Citation
Morimoto, M., Choi, K., Boerkoel, C.F., Cho, K.S. (2016). Chromatin changes in SMARCAL1 deficiency: A hypothesis for the gene expression alterations of Schimke immuno-osseous dysplasia.  Nucleus 7(6): 560--571.
FlyBase ID
FBrf0234417
Publication Type
Research paper
Abstract

Mutations in SMARCAL1, which encodes a DNA annealing helicase with roles in DNA replication fork restart, DNA repair, and gene expression modulation, cause Schimke immuno-osseous dysplasia (SIOD), an autosomal recessive disease characterized by skeletal dysplasia, renal disease, T-cell immunodeficiency, and arteriosclerosis. The clinical features of SIOD arise from pathological changes in gene expression; however, the underlying mechanism for these gene expression alterations remains unclear. We hypothesized that changes of the epigenome alter gene expression in SIOD. To test this, we performed a genetic screen for interaction between Marcal1, the Drosophila melanogaster ortholog of SMARCAL1, and the genes of the trithorax group (trxG) and Polycomb group (PcG), which encode epigenetic regulators. SMARCAL1 and Marcal1 genetically interacted with trxG and PcG members. A homozygous null mutation of Marcal1 suppressed the wing-to-haltere transformation, ectopic Ultrabithorax (Ubx) expression, and ectopic Ubx minigene expression caused by PcG deficiency. The suppression of ectopic Ubx expression correlated with reduced chromatin accessibility of the Ubx promoter. To our knowledge, this is the first in vivo evidence for deficiency of a SMARCAL1 ortholog altering the chromatin structure of a gene.

PubMed ID
PubMed Central ID
PMC5215361 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nucleus
    Title
    Nucleus
    ISBN/ISSN
    1949-1034 1949-1042
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