title: Systems genetics implicates cytoskeletal genes in oocyte control of cloned embryo quality.
abstract: Cloning by somatic cell nuclear transfer is an important technology, but remains limited due to poor rates of success. Identifying genes supporting clone development would enhance our understanding of basic embryology, improve applications of the technology, support greater understanding of establishing pluripotent stem cells, and provide new insight into clinically important determinants of oocyte quality. For the first time, a systems genetics approach was taken to discover genes contributing to the ability of an oocyte to support early cloned embryo development. This identified a primary locus on mouse chromosome 17 and potential loci on chromosomes 1 and 4. A combination of oocyte transcriptome profiling data, expression correlation analysis, and functional and network analyses yielded a short list of likely candidate genes in two categories. The major category-including two genes with the strongest genetic associations with the traits (Epb4.1l3 and Dlgap1)-encodes proteins associated with the subcortical cytoskeleton and other cytoskeletal elements such as the spindle. The second category encodes chromatin and transcription regulators (Runx1t1, Smchd1, and Chd7). Smchd1 promotes X chromosome inactivation, whereas Chd7 regulates expression of pluripotency genes. Runx1t1 has not been associated with these processes, but acts as a transcriptional repressor. The finding that cytoskeleton-associated proteins may be key determinants of early clone development highlights potential roles for cytoplasmic components of the oocyte in supporting nuclear reprogramming. The transcriptional regulators identified may contribute to the overall process as downstream effectors.
authors: The Fels Institute for Cancer Research and Molecular Biology, Philadelphia, PA 19140, USA.
authors: Yong
authors: Y
authors: Cheng
authors: John
authors: J
authors: Gaughan
authors: Uros
authors: U
authors: Midic
authors: Zhiming
authors: Z
authors: Han
authors: Cheng-Guang
authors: CG
authors: Liang
authors: Bela G
authors: BG
authors: Patel
authors: Keith E
authors: KE
authors: Latham
mesh_terms: D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D002875:Chromosomes; D019976:Cloning, Organism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D053652:Nuclear Transfer Techniques; D009865:Oocytes / Q000378:metabolism*; D040641:Quantitative Trait Loci; D000074407:SAP90-PSD95 Associated Proteins; D008941:Spindle Apparatus / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: C507367:Chd7 protein, mouse; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C000614190:Dlgap1 protein, mouse; C488402:Epb41l3 protein, mouse; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D000074407:SAP90-PSD95 Associated Proteins; C529024:SmcHD1 protein, mouse; D014157:Transcription Factors