Publications by authors named "Yoshiko Mito"

5 Publications

  • Page 1 of 1

Intragenic CNTN4 copy number variants associated with a spectrum of neurobehavioral phenotypes.

Eur J Med Genet 2020 Mar 15;63(3):103736. Epub 2019 Aug 15.

Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:

Deletions and duplications involving the CNTN4 gene, which encodes for the contactin 4 protein, have been reported in children with autism spectrum disorder (ASD) and other neurodevelopmental phenotypes. In this study, we performed clinical and genetic characterization of three individuals from unrelated families with copy number variants (CNV) (one deletion and two duplications) within CNTN4. The patients exhibited cognitive delay (3/3), growth restriction (3/3), motor delay (2/3), and febrile seizure/epilepsy (2/3). In contrast to previous reports, all probands presented with speech apraxia or delay with no diagnosis of ASD. Parental studies for the proband with the deletion and one of the 2 probands with the duplication revealed paternal origin of the CNTN4 CNV. Interestingly, previously documented CNV involving this gene were mostly inherited from unaffected fathers, raising questions regarding reduced penetrance and potential parent-of-origin effect. Our findings are compared with previously reported patients and patients in the DECIPHER database. The speech impairment in the three probands suggests a role for CNTN4 in language development. We discuss potential factors contributing to phenotypic heterogeneity and reduced penetrance and attempt to find possible genotype-phenotype correlation. Larger cohorts are needed for comprehensive and unbiased phenotyping and molecular characterization that may lead to better understanding of the underlying mechanisms of reduced penetrance, variable expressivity, and potential parent-of-origin effect of copy number variants encompassing CNTN4.
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http://dx.doi.org/10.1016/j.ejmg.2019.103736DOI Listing
March 2020

[Histone turnover in the dynamic regulation of chromatin].

Authors:
Yoshiko Mito

Tanpakushitsu Kakusan Koso 2008 Apr;53(5):658-65

Fred Hutchinson Cancer Research Center, USA.

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April 2008

Histone replacement marks the boundaries of cis-regulatory domains.

Science 2007 Mar;315(5817):1408-11

Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.

Cellular memory is maintained at homeotic genes by cis-regulatory elements whose mechanism of action is unknown. We have examined chromatin at Drosophila homeotic gene clusters by measuring, at high resolution, levels of histone replacement and nucleosome occupancy. Homeotic gene clusters display conspicuous peaks of histone replacement at boundaries of cis-regulatory domains superimposed over broad regions of low replacement. Peaks of histone replacement closely correspond to nuclease-hypersensitive sites, binding sites for Polycomb and trithorax group proteins, and sites of nucleosome depletion. Our results suggest the existence of a continuous process that disrupts nucleosomes and maintains accessibility of cis-regulatory elements.
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http://dx.doi.org/10.1126/science.1134004DOI Listing
March 2007

Genome-scale profiling of histone H3.3 replacement patterns.

Nat Genet 2005 Oct 11;37(10):1090-7. Epub 2005 Sep 11.

Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA.

Histones of multicellular organisms are assembled into chromatin primarily during DNA replication. When chromatin assembly occurs at other times, the histone H3.3 variant replaces canonical H3. Here we introduce a new strategy for profiling epigenetic patterns on the basis of H3.3 replacement, using microarrays covering roughly one-third of the Drosophila melanogaster genome at 100-bp resolution. We identified patterns of H3.3 replacement over active genes and transposons. H3.3 replacement occurred prominently at sites of abundant RNA polymerase II and methylated H3 Lys4 throughout the genome and was enhanced on the dosage-compensated male X chromosome. Active genes were depleted of histones at promoters and were enriched in H3.3 from upstream to downstream of transcription units. We propose that deposition and inheritance of actively modified H3.3 in regulatory regions maintains transcriptionally active chromatin.
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http://dx.doi.org/10.1038/ng1637DOI Listing
October 2005

Distinct developmental function of two Caenorhabditis elegans homologs of the cohesin subunit Scc1/Rad21.

Mol Biol Cell 2003 Jun 6;14(6):2399-409. Epub 2003 Feb 6.

Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Japan.

Cohesin, which mediates sister chromatid cohesion, is composed of four subunits, named Scc1/Rad21, Scc3, Smc1, and Smc3 in yeast. Caenorhabditis elegans has a single homolog for each of Scc3, Smc1, and Smc3, but as many as four for Scc1/Rad21 (COH-1, SCC-1/COH-2, COH-3, and REC-8). Except for REC-8 required for meiosis, function of these C. elegans proteins remains largely unknown. Herein, we examined their possible involvement in mitosis and development. Embryos depleted of the homolog of either Scc3, or Smc1, or Smc3 by RNA interference revealed a defect in mitotic chromosome segregation but not in chromosome condensation and cytokinesis. Depletion of SCC-1/COH-2 caused similar phenotypes. SCC-1/COH-2 was present in cells destined to divide. It localized to chromosomes in a cell cycle-dependent manner. Worms depleted of COH-1 arrested at either the late embryonic or the larval stage, with no indication of mitotic dysfunction. COH-1 associated chromosomes throughout the cell cycle in all somatic cells undergoing late embryogenesis or larval development. Thus, SCC-1/COH-2 and the homologs of Scc3, Smc1, and Smc3 facilitate mitotic chromosome segregation during the development, presumably by forming a cohesin complex, whereas COH-1 seems to play a role important for development but unrelated to mitosis.
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http://dx.doi.org/10.1091/mbc.e02-09-0603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC194888PMC
June 2003
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