8 results on '"Yuki Horisawa-Takada"'
Search Results
2. KCTD19 and its associated protein ZFP541 are independently essential for meiosis in male mice.
- Author
-
Seiya Oura, Takayuki Koyano, Chisato Kodera, Yuki Horisawa-Takada, Makoto Matsuyama, Kei-Ichiro Ishiguro, and Masahito Ikawa
- Subjects
Genetics ,QH426-470 - Abstract
Meiosis is a cell division process with complex chromosome events where various molecules must work in tandem. To find meiosis-related genes, we screened evolutionarily conserved and reproductive tract-enriched genes using the CRISPR/Cas9 system and identified potassium channel tetramerization domain containing 19 (Kctd19) as an essential factor for meiosis. In prophase I, Kctd19 deficiency did not affect synapsis or the DNA damage response, and chiasma structures were also observed in metaphase I spermatocytes of Kctd19 KO mice. However, spermatocytes underwent apoptotic elimination during the metaphase-anaphase transition. We were able to rescue the Kctd19 KO phenotype with an epitope-tagged Kctd19 transgene. By immunoprecipitation-mass spectrometry, we confirmed the association of KCTD19 with zinc finger protein 541 (ZFP541) and histone deacetylase 1 (HDAC1). Phenotyping of Zfp541 KO spermatocytes demonstrated XY chromosome asynapsis and recurrent DNA damage in the late pachytene stage, leading to apoptosis. In summary, our study reveals that KCTD19 associates with ZFP541 and HDAC1, and that both KCTD19 and ZFP541 are essential for meiosis in male mice.
- Published
- 2021
- Full Text
- View/download PDF
3. Meiotic cohesins mediate initial loading of HORMAD1 to the chromosomes and coordinate SC formation during meiotic prophase.
- Author
-
Yasuhiro Fujiwara, Yuki Horisawa-Takada, Erina Inoue, Naoki Tani, Hiroki Shibuya, Sayoko Fujimura, Ryo Kariyazono, Toyonori Sakata, Kunihiro Ohta, Kimi Araki, Yuki Okada, and Kei-Ichiro Ishiguro
- Subjects
Genetics ,QH426-470 - Abstract
During meiotic prophase, sister chromatids are organized into axial element (AE), which underlies the structural framework for the meiotic events such as meiotic recombination and homolog synapsis. HORMA domain-containing proteins (HORMADs) localize along AE and play critical roles in the regulation of those meiotic events. Organization of AE is attributed to two groups of proteins: meiotic cohesins REC8 and RAD21L; and AE components SYCP2 and SYCP3. It has been elusive how these chromosome structural proteins contribute to the chromatin loading of HORMADs prior to AE formation. Here we newly generated Sycp2 null mice and showed that initial chromatin loading of HORMAD1 was mediated by meiotic cohesins prior to AE formation. HORMAD1 interacted not only with the AE components SYCP2 and SYCP3 but also with meiotic cohesins. Notably, HORMAD1 interacted with meiotic cohesins even in Sycp2-KO, and localized along cohesin axial cores independently of the AE components SYCP2 and SYCP3. Hormad1/Rad21L-double knockout (dKO) showed more severe defects in the formation of synaptonemal complex (SC) compared to Hormad1-KO or Rad21L-KO. Intriguingly, Hormad1/Rec8-dKO but not Hormad1/Rad21L-dKO showed precocious separation of sister chromatid axis. These findings suggest that meiotic cohesins REC8 and RAD21L mediate chromatin loading and the mode of action of HORMAD1 for synapsis during early meiotic prophase.
- Published
- 2020
- Full Text
- View/download PDF
4. KCTD19 associates with ZFP541 and HDAC1 and is required for meiotic exit in male mice
- Author
-
Seiya Oura, Takayuki Koyano, Yuki Horisawa-Takada, Kei-ichiro Ishiguro, Chisato Kodera, Masahito Ikawa, and Makoto Matsuyama
- Subjects
Chromosome segregation ,Meiosis ,Cell division ,Homologous chromosome ,Synapsis ,Chromosome ,Biology ,Homologous recombination ,Chiasma ,Cell biology - Abstract
Meiosis is a cell division process with complex chromosome events where various molecules must work in tandem. To find meiosis-related genes, we screened evolutionarily conserved and reproductive tract-enriched genes using the CRISPR/Cas9 system and identified potassium channel tetramerization domain containing 19 (Kctd19) as an essential factor for meiosis. In prophase I, Kctd19 deficiency did not affect synapsis or the DNA damage response, and chiasma structures were also observed in metaphase I spermatocytes of Kctd19 KO mice. However, spermatocytes underwent apoptotic elimination during the metaphase-anaphase transition. We were able to rescue the Kctd19 KO phenotype with an epitope-tagged Kctd19 transgene. Immunoprecipitation-mass spectrometry identified zinc finger protein 541 (ZFP541) and histone deacetylase 1 (HDAC1) as binding partners of KCTD19, indicating that KCTD19 is involved in chromatin modification. Phenotyping of Zfp541 KO spermatocytes demonstrated XY chromosome asynapsis and recurrent DNA damage in the late pachytene stage, leading to apoptosis. In summary, our study reveals that KCTD19 associates with ZFP541 and HDAC1, and that both KCTD19 and ZFP541 were essential for meiotic exit in male mice.Author summaryMeiosis is a fundamental process that consisting of one round of genomic DNA replication and two rounds of chromosome segregation producing four haploid cells. To properly distribute their genetic material, cells need to undergo complex chromosome events such as a physical linkage of homologous chromosomes (termed synapsis) and meiotic recombination. The molecules involved in these events have not been fully characterized yet, especially in mammals. Using a CRISPR/Cas9-screening system, we identified the potassium channel tetramerization domain containing 19 (Kctd19) as an essential factor for meiosis in male mice. Further, we identified zinc finger protein 541 (ZFP541) and histone deacetylase 1 (HDAC1) as binding partners of KCTD19. By observing meiosis of Zfp541 knockout germ cells, we found that Zfp541 was also essential for meiotic completion. These results show that the KCTD19/ZFP541 complex plays a critical role and is indispensable for male meiosis and fertility.
- Published
- 2021
5. KCTD19 and its associated protein ZFP541 are independently essential for meiosis in male mice
- Author
-
Chisato Kodera, Kei-ichiro Ishiguro, Takayuki Koyano, Masahito Ikawa, Makoto Matsuyama, Seiya Oura, and Yuki Horisawa-Takada
- Subjects
Male ,Cancer Research ,Cell division ,Chromosomal Proteins, Non-Histone ,Cell Cycle Proteins ,Histone Deacetylase 1 ,Apoptosis ,Immunostaining ,QH426-470 ,Mice ,0302 clinical medicine ,Spermatocytes ,Animal Cells ,Testis ,Medicine and Health Sciences ,Transgenes ,Cell Cycle and Cell Division ,Meiotic Prophase I ,Genetics (clinical) ,Conserved Sequence ,Zinc finger ,Staining ,0303 health sciences ,Genes, Essential ,Cell Death ,Chromosome Biology ,Genetically Modified Organisms ,Synapsis ,Nuclear Proteins ,Seminiferous Tubules ,Spermatids ,Chiasma ,Cell biology ,Precipitation Techniques ,Meiosis ,Phenotype ,Cell Processes ,Engineering and Technology ,Cellular Types ,Anatomy ,Genetic Engineering ,Genital Anatomy ,Research Article ,Biotechnology ,DNA damage ,Bioengineering ,Biology ,Research and Analysis Methods ,Evolution, Molecular ,03 medical and health sciences ,Genetics ,Animals ,Immunoprecipitation ,Molecular Biology ,Metaphase ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,Cell Nucleus ,Genetically Modified Animals ,Reproductive System ,Chromosome ,Biology and Life Sciences ,Cell Biology ,Sperm ,Chromosome Pairing ,Fertility ,Germ Cells ,Specimen Preparation and Treatment ,Pachytene Stage ,CRISPR-Cas Systems ,Anaphase ,030217 neurology & neurosurgery ,DNA Damage ,Transcription Factors - Abstract
Meiosis is a cell division process with complex chromosome events where various molecules must work in tandem. To find meiosis-related genes, we screened evolutionarily conserved and reproductive tract-enriched genes using the CRISPR/Cas9 system and identified potassium channel tetramerization domain containing 19 (Kctd19) as an essential factor for meiosis. In prophase I, Kctd19 deficiency did not affect synapsis or the DNA damage response, and chiasma structures were also observed in metaphase I spermatocytes of Kctd19 KO mice. However, spermatocytes underwent apoptotic elimination during the metaphase-anaphase transition. We were able to rescue the Kctd19 KO phenotype with an epitope-tagged Kctd19 transgene. By immunoprecipitation-mass spectrometry, we confirmed the association of KCTD19 with zinc finger protein 541 (ZFP541) and histone deacetylase 1 (HDAC1). Phenotyping of Zfp541 KO spermatocytes demonstrated XY chromosome asynapsis and recurrent DNA damage in the late pachytene stage, leading to apoptosis. In summary, our study reveals that KCTD19 associates with ZFP541 and HDAC1, and that both KCTD19 and ZFP541 are essential for meiosis in male mice., Author summary Meiosis is a fundamental process that consists of one round of genomic DNA replication and two rounds of chromosome segregation, producing four haploid cells. To properly distribute their genetic material, cells need to undergo complex chromosome events such as a physical linkage of homologous chromosomes (termed synapsis) and meiotic recombination. The molecules involved in these events have not been fully characterized yet, especially in mammals. Using a CRISPR/Cas9-screening system, we identified the potassium channel tetramerization domain containing 19 (Kctd19) as an essential factor for meiosis in male mice. Further, we confirmed the association of KCTD19 with zinc finger protein 541 (ZFP541) and histone deacetylase 1 (HDAC1). By observing meiosis of Zfp541 knockout germ cells, we found that Zfp541 was also essential for meiosis. These results show that the KCTD19/ZFP541 complex plays a critical role and is indispensable for male meiosis and fertility.
- Published
- 2021
6. Meiosis-specific ZFP541 repressor complex promotes meiotic prophase exit during spermatogenesis
- Author
-
Kazumasa Takemoto, Chisato Kodera, Sayoko Fujimura, Takashi Ohba, Hitoshi Niwa, Naoki Tani, Kimi Araki, Shingo Usuki, Ryuki Shimada, Akihiko Sakashita, Atsushi Suzuki, Yuki Horisawa-Takada, Kei-ichiro Ishiguro, Makoto Tachibana, Tomohiko Akiyama, Ryo Maeda, Hidetaka Katabuchi, Satoshi H. Namekawa, Kumi Matsuura, and Kenichi Horisawa
- Subjects
Prophase ,Meiosis ,Gene expression ,Transcriptional regulation ,Repressor ,Biology ,Gene ,Covalent chromatin modification ,Cell biology ,Chromatin - Abstract
SummaryDuring spermatogenesis, meiosis is accompanied by robust alteration in gene expression and chromatin status. However, it remained elusive how meiotic transcriptional program is established to ensure completion of meiotic prophase. Here, we identified a novel protein complex consisting of germ-cell-specific zinc-finger protein ZFP541 and its interactor KCTD19 as the key transcriptional regulator for meiotic prophase exit. Our genetic study showed that ZFP541 and KCTD19 are co-expressed from pachytene onward and play an essential role in the completion of meiotic prophase program in the testis. Furthermore, our ChIP-seq and transcriptome analyses revealed that ZFP541 binds to and suppresses a broad range of genes whose function is associated with biological processes of transcriptional regulation and covalent chromatin modification. The present study demonstrated that germ-cell specific ZFP541-KCTD19 containing complex promotes meiotic prophase exit in males, and triggers reconstruction of the transcription network and chromatin organization leading to post-meiotic development.
- Published
- 2021
7. Meiosis-specific ZFP541 repressor complex promotes developmental progression of meiotic prophase towards completion during mouse spermatogenesis
- Author
-
Chisato Kodera, Akihiko Sakashita, Kazumasa Takemoto, Atsushi Suzuki, Ryo Maeda, Satoshi H. Namekawa, Kimi Araki, Takashi Ohba, Shingo Usuki, Naoki Tani, Yuki Horisawa-Takada, Kumi Matsuura, Ryuki Shimada, Kenichi Horisawa, Tomohiko Akiyama, Kei-ichiro Ishiguro, Sayoko Fujimura, Hitoshi Niwa, Hidetaka Katabuchi, and Makoto Tachibana
- Subjects
0301 basic medicine ,Male ,Potassium Channels ,Transcription, Genetic ,Chromosomal Proteins, Non-Histone ,General Physics and Astronomy ,Histone Deacetylase 2 ,Cell Cycle Proteins ,Histone Deacetylase 1 ,Covalent chromatin modification ,Transcriptome ,Mice ,0302 clinical medicine ,Transcriptional regulation ,RNA-Seq ,Mice, Knockout ,Multidisciplinary ,Voltage-Gated ,Nuclear Proteins ,Spermatids ,Chromatin ,Cell biology ,Chromosomal Proteins ,Meiosis ,Potassium Channels, Voltage-Gated ,Chromatin Immunoprecipitation Sequencing ,Stem Cell Research - Nonembryonic - Non-Human ,Female ,Transcription ,Biotechnology ,Science ,Knockout ,1.1 Normal biological development and functioning ,Repressor ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Prophase ,Genetic ,Underpinning research ,Genetics ,Animals ,Humans ,Spermatogenesis ,Gene ,Infertility, Male ,urogenital system ,Animal ,Contraception/Reproduction ,fungi ,Human Genome ,General Chemistry ,Non-Histone ,Stem Cell Research ,Disease Models, Animal ,030104 developmental biology ,Infertility ,Disease Models ,Oocytes ,Pachytene Stage ,030217 neurology & neurosurgery ,Transcription Factors - Abstract
During spermatogenesis, meiosis is accompanied by a robust alteration in gene expression and chromatin status. However, it remains elusive how the meiotic transcriptional program is established to ensure completion of meiotic prophase. Here, we identify a protein complex that consists of germ-cell-specific zinc-finger protein ZFP541 and its interactor KCTD19 as the key transcriptional regulators in mouse meiotic prophase progression. Our genetic study shows that ZFP541 and KCTD19 are co-expressed from pachytene onward and play an essential role in the completion of the meiotic prophase program in the testis. Furthermore, our ChIP-seq and transcriptome analyses identify that ZFP541 binds to and suppresses a broad range of genes whose function is associated with biological processes of transcriptional regulation and covalent chromatin modification. The present study demonstrates that a germ-cell specific complex that contains ZFP541 and KCTD19 promotes the progression of meiotic prophase towards completion in male mice, and triggers the reconstruction of the transcriptional network and chromatin organization leading to post-meiotic development., The authors add to our knowledge of the transcriptional regulation of the meiotic program in mice spermatocytes, showing ZFP541 regulates meiotic prophase and transition to the division phase by being the target for upstream factors MEIOSIN/STRA8.
- Published
- 2021
8. Meiotic cohesins mediate initial loading of HORMAD1 to the chromosomes and coordinate SC formation during meiotic prophase
- Author
-
Sayoko Fujimura, Erina Inoue, Toyonori Sakata, Kei-ichiro Ishiguro, Yuki Okada, Naoki Tani, Yuki Horisawa-Takada, Hiroki Shibuya, Kunihiro Ohta, Yasuhiro Fujiwara, Kimi Araki, and Ryo Kariyazono
- Subjects
Male ,Cancer Research ,Chromosomal Proteins, Non-Histone ,Gene Expression ,Cell Cycle Proteins ,QH426-470 ,Prophase ,Mice ,0302 clinical medicine ,Animal Cells ,Spermatocytes ,Medicine and Health Sciences ,Cell Cycle and Cell Division ,Testes ,Genetics (clinical) ,Staining ,Mice, Knockout ,0303 health sciences ,Chromosome Biology ,Synaptonemal Complex ,Synapsis ,Nuclear Proteins ,Chromatin ,Cell biology ,Precipitation Techniques ,DNA-Binding Proteins ,Synaptonemal complex ,Meiosis ,Cell Processes ,Chromatid ,Epigenetics ,Female ,Cellular Types ,Anatomy ,biological phenomena, cell phenomena, and immunity ,Genital Anatomy ,Research Article ,Biology ,Chromatids ,Research and Analysis Methods ,Chromosomes ,03 medical and health sciences ,Genetics ,Sister chromatids ,Immunoprecipitation ,Animals ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,Cohesin ,urogenital system ,Reproductive System ,Biology and Life Sciences ,Chromosome Staining ,Cell Biology ,Phosphoproteins ,Sperm ,Mice, Inbred C57BL ,Germ Cells ,Specimen Preparation and Treatment ,030217 neurology & neurosurgery ,Meiotic Prophase - Abstract
During meiotic prophase, sister chromatids are organized into axial element (AE), which underlies the structural framework for the meiotic events such as meiotic recombination and homolog synapsis. HORMA domain-containing proteins (HORMADs) localize along AE and play critical roles in the regulation of those meiotic events. Organization of AE is attributed to two groups of proteins: meiotic cohesins REC8 and RAD21L; and AE components SYCP2 and SYCP3. It has been elusive how these chromosome structural proteins contribute to the chromatin loading of HORMADs prior to AE formation. Here we newly generated Sycp2 null mice and showed that initial chromatin loading of HORMAD1 was mediated by meiotic cohesins prior to AE formation. HORMAD1 interacted not only with the AE components SYCP2 and SYCP3 but also with meiotic cohesins. Notably, HORMAD1 interacted with meiotic cohesins even in Sycp2-KO, and localized along cohesin axial cores independently of the AE components SYCP2 and SYCP3. Hormad1/Rad21L-double knockout (dKO) showed more severe defects in the formation of synaptonemal complex (SC) compared to Hormad1-KO or Rad21L-KO. Intriguingly, Hormad1/Rec8-dKO but not Hormad1/Rad21L-dKO showed precocious separation of sister chromatid axis. These findings suggest that meiotic cohesins REC8 and RAD21L mediate chromatin loading and the mode of action of HORMAD1 for synapsis during early meiotic prophase., Author summary During meiotic prophase, homologous chromosomes undergo pairing/synapsis. HORMA domain-containing proteins (HORMAD1, HORMAD2) localize along unsynapsed chromosome axis and monitor homolog synapsis. However, molecular mechanisms how mouse HORMA domain-containing proteins that do not contain a definitive DNA-binding domain localize to the axis chromosome remains elusive. In particular, because chromosome axis is generated by meiotic cohesins (RAD21L, REC8) and axial element (AE) components (SYCP2, SYCP3), it has been elusive how those chromosome structural proteins contribute to the loading of HORMAD proteins onto the chromosomes. This was due to the unavailability of Sycp2 KO mouse that should allow deep analysis of chromosome dynamics in the complete absence of AE. To solve this issue, in the present study, we newly generated Sycp2 null mice, in which AE structure was completely abolished. This allowed us to assess meiotic cohesins and AE components separately, in terms of their roles on chromatin loading of HORMAD proteins. The most notable among our findings is that the localization of HORMAD1 on the chromatin is initially mediated through meiotic cohesins prior to axis formation. Intriguingly, our genetic study suggests that HORMAD1 in collaboration with meiotic cohesins plays distinct roles in sister chromatid cohesion, homolog synapsis and meiotic recombination during the early meiotic prophase.
- Published
- 2020
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.