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Fuyuki Ishikawa - One of the best experts on this subject based on the ideXlab platform.

  • uhrf1 dependent h3k23 ubiquitylation couples maintenance DNA Methylation and replication
    Nature, 2013
    Co-Authors: Atsuya Nishiyama, Luna Yamaguchi, Yoshikazu Johmura, Kyohei Arita, Jafar Sharif, Takeshi Kawamura, Keiko Nakanishi, Shintaro Shimamura, Tatsuhiko Kodama, Fuyuki Ishikawa
    Abstract:

    The RING finger domain protein Uhrf1 is known to have an important role in DNA Methylation pattern maintenance through the recruitment of the methyltransferase Dnmt1 to hemimethylated DNA sites: here, Uhrf1 is shown to act as a ubiquitin ligase for H3, an essential step in Dnmt1 recruitment. The RING finger domain protein Uhrf1 has an essential role in maintaining patterns of DNA Methylation during replication by recruiting the DNA methyltransferase Dnmt1 to hemi-methylated DNA sites. Here, Makoto Nakanishi and colleagues reproduce maintenance DNA Methylation in an in vitro system using Xenopus egg extracts. They show that Uhrf1 is an E3 ubiquitin ligase for histone H3, and that ubiquitination of H3 is required for the recruitment of Dnmt1 to DNA replication sites. Faithful propagation of DNA Methylation patterns during DNA replication is critical for maintaining cellular phenotypes of individual differentiated cells1,2,3,4,5. Although it is well established that Uhrf1 (ubiquitin-like with PHD and ring finger domains 1; also known as Np95 and ICBP90) specifically binds to hemi-methylated DNA through its SRA (SET and RING finger associated) domain and has an essential role in maintenance of DNA Methylation by recruiting Dnmt1 to hemi-methylated DNA sites6,7,8,9,10, the mechanism by which Uhrf1 coordinates the maintenance of DNA Methylation and DNA replication is largely unknown. Here we show that Uhrf1-dependent histone H3 ubiquitylation has a prerequisite role in the maintenance DNA Methylation. Using Xenopus egg extracts, we successfully reproduce maintenance DNA Methylation in vitro. Dnmt1 depletion results in a marked accumulation of Uhrf1-dependent ubiquitylation of histone H3 at lysine 23. Dnmt1 preferentially associates with ubiquitylated H3 in vitro though a region previously identified as a replication foci targeting sequence11. The RING finger mutant of Uhrf1 fails to recruit Dnmt1 to DNA replication sites and maintain DNA Methylation in mammalian cultured cells. Our findings represent the first evidence, to our knowledge, of the mechanistic link between DNA Methylation and DNA replication through histone H3 ubiquitylation.

  • uhrf1 dependent h3k23 ubiquitylation couples maintenance DNA Methylation and replication
    Nature, 2013
    Co-Authors: Atsuya Nishiyama, Luna Yamaguchi, Yoshikazu Johmura, Kyohei Arita, Jafar Sharif, Takeshi Kawamura, Keiko Nakanishi, Shintaro Shimamura, Tatsuhiko Kodama, Fuyuki Ishikawa
    Abstract:

    Faithful propagation of DNA Methylation patterns during DNA replication is critical for maintaining cellular phenotypes of individual differentiated cells. Although it is well established that Uhrf1 (ubiquitin-like with PHD and ring finger domains 1; also known as Np95 and ICBP90) specifically binds to hemi-methylated DNA through its SRA (SET and RING finger associated) domain and has an essential role in maintenance of DNA Methylation by recruiting Dnmt1 to hemi-methylated DNA sites, the mechanism by which Uhrf1 coordinates the maintenance of DNA Methylation and DNA replication is largely unknown. Here we show that Uhrf1-dependent histone H3 ubiquitylation has a prerequisite role in the maintenance DNA Methylation. Using Xenopus egg extracts, we successfully reproduce maintenance DNA Methylation in vitro. Dnmt1 depletion results in a marked accumulation of Uhrf1-dependent ubiquitylation of histone H3 at lysine 23. Dnmt1 preferentially associates with ubiquitylated H3 in vitro though a region previously identified as a replication foci targeting sequence. The RING finger mutant of Uhrf1 fails to recruit Dnmt1 to DNA replication sites and maintain DNA Methylation in mammalian cultured cells. Our findings represent the first evidence, to our knowledge, of the mechanistic link between DNA Methylation and DNA replication through histone H3 ubiquitylation.

Atsuya Nishiyama - One of the best experts on this subject based on the ideXlab platform.

  • Usp7-dependent histone H3 deubiquitylation regulates maintenance of DNA Methylation.
    Scientific reports, 2017
    Co-Authors: Luna Yamaguchi, Atsuya Nishiyama, Toshinori Misaki, Yoshikazu Johmura, Jun Ueda, Kyohei Arita, Koji Nagao, Chikashi Obuse, Makoto Nakanishi
    Abstract:

    Uhrf1-dependent histone H3 ubiquitylation plays a crucial role in the maintenance of DNA Methylation via the recruitment of the DNA methyltransferase Dnmt1 to DNA Methylation sites. However, the involvement of deubiquitylating enzymes (DUBs) targeting ubiquitylated histone H3 in the maintenance of DNA Methylation is largely unknown. With the use of Xenopus egg extracts, we demonstrate here that Usp7, a ubiquitin carboxyl-terminal hydrolase, forms a stable complex with Dnmt1 and is recruited to DNA Methylation sites during DNA replication. Usp7 deubiquitylates ubiquitylated histone H3 in vitro. Inhibition of Usp7 activity or its depletion in egg extracts results in enhanced and extended binding of Dnmt1 to chromatin, suppressing DNA Methylation. Depletion of Usp7 in HeLa cells causes enhanced histone H3 ubiquitylation and enlargement of Dnmt1 nuclear foci during DNA replication. Our results thus suggest that Usp7 is a key factor that regulates maintenance of DNA Methylation.

  • uhrf1 dependent h3k23 ubiquitylation couples maintenance DNA Methylation and replication
    Nature, 2013
    Co-Authors: Atsuya Nishiyama, Luna Yamaguchi, Yoshikazu Johmura, Kyohei Arita, Jafar Sharif, Takeshi Kawamura, Keiko Nakanishi, Shintaro Shimamura, Tatsuhiko Kodama, Fuyuki Ishikawa
    Abstract:

    The RING finger domain protein Uhrf1 is known to have an important role in DNA Methylation pattern maintenance through the recruitment of the methyltransferase Dnmt1 to hemimethylated DNA sites: here, Uhrf1 is shown to act as a ubiquitin ligase for H3, an essential step in Dnmt1 recruitment. The RING finger domain protein Uhrf1 has an essential role in maintaining patterns of DNA Methylation during replication by recruiting the DNA methyltransferase Dnmt1 to hemi-methylated DNA sites. Here, Makoto Nakanishi and colleagues reproduce maintenance DNA Methylation in an in vitro system using Xenopus egg extracts. They show that Uhrf1 is an E3 ubiquitin ligase for histone H3, and that ubiquitination of H3 is required for the recruitment of Dnmt1 to DNA replication sites. Faithful propagation of DNA Methylation patterns during DNA replication is critical for maintaining cellular phenotypes of individual differentiated cells1,2,3,4,5. Although it is well established that Uhrf1 (ubiquitin-like with PHD and ring finger domains 1; also known as Np95 and ICBP90) specifically binds to hemi-methylated DNA through its SRA (SET and RING finger associated) domain and has an essential role in maintenance of DNA Methylation by recruiting Dnmt1 to hemi-methylated DNA sites6,7,8,9,10, the mechanism by which Uhrf1 coordinates the maintenance of DNA Methylation and DNA replication is largely unknown. Here we show that Uhrf1-dependent histone H3 ubiquitylation has a prerequisite role in the maintenance DNA Methylation. Using Xenopus egg extracts, we successfully reproduce maintenance DNA Methylation in vitro. Dnmt1 depletion results in a marked accumulation of Uhrf1-dependent ubiquitylation of histone H3 at lysine 23. Dnmt1 preferentially associates with ubiquitylated H3 in vitro though a region previously identified as a replication foci targeting sequence11. The RING finger mutant of Uhrf1 fails to recruit Dnmt1 to DNA replication sites and maintain DNA Methylation in mammalian cultured cells. Our findings represent the first evidence, to our knowledge, of the mechanistic link between DNA Methylation and DNA replication through histone H3 ubiquitylation.

  • uhrf1 dependent h3k23 ubiquitylation couples maintenance DNA Methylation and replication
    Nature, 2013
    Co-Authors: Atsuya Nishiyama, Luna Yamaguchi, Yoshikazu Johmura, Kyohei Arita, Jafar Sharif, Takeshi Kawamura, Keiko Nakanishi, Shintaro Shimamura, Tatsuhiko Kodama, Fuyuki Ishikawa
    Abstract:

    Faithful propagation of DNA Methylation patterns during DNA replication is critical for maintaining cellular phenotypes of individual differentiated cells. Although it is well established that Uhrf1 (ubiquitin-like with PHD and ring finger domains 1; also known as Np95 and ICBP90) specifically binds to hemi-methylated DNA through its SRA (SET and RING finger associated) domain and has an essential role in maintenance of DNA Methylation by recruiting Dnmt1 to hemi-methylated DNA sites, the mechanism by which Uhrf1 coordinates the maintenance of DNA Methylation and DNA replication is largely unknown. Here we show that Uhrf1-dependent histone H3 ubiquitylation has a prerequisite role in the maintenance DNA Methylation. Using Xenopus egg extracts, we successfully reproduce maintenance DNA Methylation in vitro. Dnmt1 depletion results in a marked accumulation of Uhrf1-dependent ubiquitylation of histone H3 at lysine 23. Dnmt1 preferentially associates with ubiquitylated H3 in vitro though a region previously identified as a replication foci targeting sequence. The RING finger mutant of Uhrf1 fails to recruit Dnmt1 to DNA replication sites and maintain DNA Methylation in mammalian cultured cells. Our findings represent the first evidence, to our knowledge, of the mechanistic link between DNA Methylation and DNA replication through histone H3 ubiquitylation.

Luna Yamaguchi - One of the best experts on this subject based on the ideXlab platform.

  • Usp7-dependent histone H3 deubiquitylation regulates maintenance of DNA Methylation.
    Scientific reports, 2017
    Co-Authors: Luna Yamaguchi, Atsuya Nishiyama, Toshinori Misaki, Yoshikazu Johmura, Jun Ueda, Kyohei Arita, Koji Nagao, Chikashi Obuse, Makoto Nakanishi
    Abstract:

    Uhrf1-dependent histone H3 ubiquitylation plays a crucial role in the maintenance of DNA Methylation via the recruitment of the DNA methyltransferase Dnmt1 to DNA Methylation sites. However, the involvement of deubiquitylating enzymes (DUBs) targeting ubiquitylated histone H3 in the maintenance of DNA Methylation is largely unknown. With the use of Xenopus egg extracts, we demonstrate here that Usp7, a ubiquitin carboxyl-terminal hydrolase, forms a stable complex with Dnmt1 and is recruited to DNA Methylation sites during DNA replication. Usp7 deubiquitylates ubiquitylated histone H3 in vitro. Inhibition of Usp7 activity or its depletion in egg extracts results in enhanced and extended binding of Dnmt1 to chromatin, suppressing DNA Methylation. Depletion of Usp7 in HeLa cells causes enhanced histone H3 ubiquitylation and enlargement of Dnmt1 nuclear foci during DNA replication. Our results thus suggest that Usp7 is a key factor that regulates maintenance of DNA Methylation.

  • uhrf1 dependent h3k23 ubiquitylation couples maintenance DNA Methylation and replication
    Nature, 2013
    Co-Authors: Atsuya Nishiyama, Luna Yamaguchi, Yoshikazu Johmura, Kyohei Arita, Jafar Sharif, Takeshi Kawamura, Keiko Nakanishi, Shintaro Shimamura, Tatsuhiko Kodama, Fuyuki Ishikawa
    Abstract:

    The RING finger domain protein Uhrf1 is known to have an important role in DNA Methylation pattern maintenance through the recruitment of the methyltransferase Dnmt1 to hemimethylated DNA sites: here, Uhrf1 is shown to act as a ubiquitin ligase for H3, an essential step in Dnmt1 recruitment. The RING finger domain protein Uhrf1 has an essential role in maintaining patterns of DNA Methylation during replication by recruiting the DNA methyltransferase Dnmt1 to hemi-methylated DNA sites. Here, Makoto Nakanishi and colleagues reproduce maintenance DNA Methylation in an in vitro system using Xenopus egg extracts. They show that Uhrf1 is an E3 ubiquitin ligase for histone H3, and that ubiquitination of H3 is required for the recruitment of Dnmt1 to DNA replication sites. Faithful propagation of DNA Methylation patterns during DNA replication is critical for maintaining cellular phenotypes of individual differentiated cells1,2,3,4,5. Although it is well established that Uhrf1 (ubiquitin-like with PHD and ring finger domains 1; also known as Np95 and ICBP90) specifically binds to hemi-methylated DNA through its SRA (SET and RING finger associated) domain and has an essential role in maintenance of DNA Methylation by recruiting Dnmt1 to hemi-methylated DNA sites6,7,8,9,10, the mechanism by which Uhrf1 coordinates the maintenance of DNA Methylation and DNA replication is largely unknown. Here we show that Uhrf1-dependent histone H3 ubiquitylation has a prerequisite role in the maintenance DNA Methylation. Using Xenopus egg extracts, we successfully reproduce maintenance DNA Methylation in vitro. Dnmt1 depletion results in a marked accumulation of Uhrf1-dependent ubiquitylation of histone H3 at lysine 23. Dnmt1 preferentially associates with ubiquitylated H3 in vitro though a region previously identified as a replication foci targeting sequence11. The RING finger mutant of Uhrf1 fails to recruit Dnmt1 to DNA replication sites and maintain DNA Methylation in mammalian cultured cells. Our findings represent the first evidence, to our knowledge, of the mechanistic link between DNA Methylation and DNA replication through histone H3 ubiquitylation.

  • uhrf1 dependent h3k23 ubiquitylation couples maintenance DNA Methylation and replication
    Nature, 2013
    Co-Authors: Atsuya Nishiyama, Luna Yamaguchi, Yoshikazu Johmura, Kyohei Arita, Jafar Sharif, Takeshi Kawamura, Keiko Nakanishi, Shintaro Shimamura, Tatsuhiko Kodama, Fuyuki Ishikawa
    Abstract:

    Faithful propagation of DNA Methylation patterns during DNA replication is critical for maintaining cellular phenotypes of individual differentiated cells. Although it is well established that Uhrf1 (ubiquitin-like with PHD and ring finger domains 1; also known as Np95 and ICBP90) specifically binds to hemi-methylated DNA through its SRA (SET and RING finger associated) domain and has an essential role in maintenance of DNA Methylation by recruiting Dnmt1 to hemi-methylated DNA sites, the mechanism by which Uhrf1 coordinates the maintenance of DNA Methylation and DNA replication is largely unknown. Here we show that Uhrf1-dependent histone H3 ubiquitylation has a prerequisite role in the maintenance DNA Methylation. Using Xenopus egg extracts, we successfully reproduce maintenance DNA Methylation in vitro. Dnmt1 depletion results in a marked accumulation of Uhrf1-dependent ubiquitylation of histone H3 at lysine 23. Dnmt1 preferentially associates with ubiquitylated H3 in vitro though a region previously identified as a replication foci targeting sequence. The RING finger mutant of Uhrf1 fails to recruit Dnmt1 to DNA replication sites and maintain DNA Methylation in mammalian cultured cells. Our findings represent the first evidence, to our knowledge, of the mechanistic link between DNA Methylation and DNA replication through histone H3 ubiquitylation.

Kyohei Arita - One of the best experts on this subject based on the ideXlab platform.

  • Usp7-dependent histone H3 deubiquitylation regulates maintenance of DNA Methylation.
    Scientific reports, 2017
    Co-Authors: Luna Yamaguchi, Atsuya Nishiyama, Toshinori Misaki, Yoshikazu Johmura, Jun Ueda, Kyohei Arita, Koji Nagao, Chikashi Obuse, Makoto Nakanishi
    Abstract:

    Uhrf1-dependent histone H3 ubiquitylation plays a crucial role in the maintenance of DNA Methylation via the recruitment of the DNA methyltransferase Dnmt1 to DNA Methylation sites. However, the involvement of deubiquitylating enzymes (DUBs) targeting ubiquitylated histone H3 in the maintenance of DNA Methylation is largely unknown. With the use of Xenopus egg extracts, we demonstrate here that Usp7, a ubiquitin carboxyl-terminal hydrolase, forms a stable complex with Dnmt1 and is recruited to DNA Methylation sites during DNA replication. Usp7 deubiquitylates ubiquitylated histone H3 in vitro. Inhibition of Usp7 activity or its depletion in egg extracts results in enhanced and extended binding of Dnmt1 to chromatin, suppressing DNA Methylation. Depletion of Usp7 in HeLa cells causes enhanced histone H3 ubiquitylation and enlargement of Dnmt1 nuclear foci during DNA replication. Our results thus suggest that Usp7 is a key factor that regulates maintenance of DNA Methylation.

  • uhrf1 dependent h3k23 ubiquitylation couples maintenance DNA Methylation and replication
    Nature, 2013
    Co-Authors: Atsuya Nishiyama, Luna Yamaguchi, Yoshikazu Johmura, Kyohei Arita, Jafar Sharif, Takeshi Kawamura, Keiko Nakanishi, Shintaro Shimamura, Tatsuhiko Kodama, Fuyuki Ishikawa
    Abstract:

    The RING finger domain protein Uhrf1 is known to have an important role in DNA Methylation pattern maintenance through the recruitment of the methyltransferase Dnmt1 to hemimethylated DNA sites: here, Uhrf1 is shown to act as a ubiquitin ligase for H3, an essential step in Dnmt1 recruitment. The RING finger domain protein Uhrf1 has an essential role in maintaining patterns of DNA Methylation during replication by recruiting the DNA methyltransferase Dnmt1 to hemi-methylated DNA sites. Here, Makoto Nakanishi and colleagues reproduce maintenance DNA Methylation in an in vitro system using Xenopus egg extracts. They show that Uhrf1 is an E3 ubiquitin ligase for histone H3, and that ubiquitination of H3 is required for the recruitment of Dnmt1 to DNA replication sites. Faithful propagation of DNA Methylation patterns during DNA replication is critical for maintaining cellular phenotypes of individual differentiated cells1,2,3,4,5. Although it is well established that Uhrf1 (ubiquitin-like with PHD and ring finger domains 1; also known as Np95 and ICBP90) specifically binds to hemi-methylated DNA through its SRA (SET and RING finger associated) domain and has an essential role in maintenance of DNA Methylation by recruiting Dnmt1 to hemi-methylated DNA sites6,7,8,9,10, the mechanism by which Uhrf1 coordinates the maintenance of DNA Methylation and DNA replication is largely unknown. Here we show that Uhrf1-dependent histone H3 ubiquitylation has a prerequisite role in the maintenance DNA Methylation. Using Xenopus egg extracts, we successfully reproduce maintenance DNA Methylation in vitro. Dnmt1 depletion results in a marked accumulation of Uhrf1-dependent ubiquitylation of histone H3 at lysine 23. Dnmt1 preferentially associates with ubiquitylated H3 in vitro though a region previously identified as a replication foci targeting sequence11. The RING finger mutant of Uhrf1 fails to recruit Dnmt1 to DNA replication sites and maintain DNA Methylation in mammalian cultured cells. Our findings represent the first evidence, to our knowledge, of the mechanistic link between DNA Methylation and DNA replication through histone H3 ubiquitylation.

  • uhrf1 dependent h3k23 ubiquitylation couples maintenance DNA Methylation and replication
    Nature, 2013
    Co-Authors: Atsuya Nishiyama, Luna Yamaguchi, Yoshikazu Johmura, Kyohei Arita, Jafar Sharif, Takeshi Kawamura, Keiko Nakanishi, Shintaro Shimamura, Tatsuhiko Kodama, Fuyuki Ishikawa
    Abstract:

    Faithful propagation of DNA Methylation patterns during DNA replication is critical for maintaining cellular phenotypes of individual differentiated cells. Although it is well established that Uhrf1 (ubiquitin-like with PHD and ring finger domains 1; also known as Np95 and ICBP90) specifically binds to hemi-methylated DNA through its SRA (SET and RING finger associated) domain and has an essential role in maintenance of DNA Methylation by recruiting Dnmt1 to hemi-methylated DNA sites, the mechanism by which Uhrf1 coordinates the maintenance of DNA Methylation and DNA replication is largely unknown. Here we show that Uhrf1-dependent histone H3 ubiquitylation has a prerequisite role in the maintenance DNA Methylation. Using Xenopus egg extracts, we successfully reproduce maintenance DNA Methylation in vitro. Dnmt1 depletion results in a marked accumulation of Uhrf1-dependent ubiquitylation of histone H3 at lysine 23. Dnmt1 preferentially associates with ubiquitylated H3 in vitro though a region previously identified as a replication foci targeting sequence. The RING finger mutant of Uhrf1 fails to recruit Dnmt1 to DNA replication sites and maintain DNA Methylation in mammalian cultured cells. Our findings represent the first evidence, to our knowledge, of the mechanistic link between DNA Methylation and DNA replication through histone H3 ubiquitylation.

Yoshikazu Johmura - One of the best experts on this subject based on the ideXlab platform.

  • Usp7-dependent histone H3 deubiquitylation regulates maintenance of DNA Methylation.
    Scientific reports, 2017
    Co-Authors: Luna Yamaguchi, Atsuya Nishiyama, Toshinori Misaki, Yoshikazu Johmura, Jun Ueda, Kyohei Arita, Koji Nagao, Chikashi Obuse, Makoto Nakanishi
    Abstract:

    Uhrf1-dependent histone H3 ubiquitylation plays a crucial role in the maintenance of DNA Methylation via the recruitment of the DNA methyltransferase Dnmt1 to DNA Methylation sites. However, the involvement of deubiquitylating enzymes (DUBs) targeting ubiquitylated histone H3 in the maintenance of DNA Methylation is largely unknown. With the use of Xenopus egg extracts, we demonstrate here that Usp7, a ubiquitin carboxyl-terminal hydrolase, forms a stable complex with Dnmt1 and is recruited to DNA Methylation sites during DNA replication. Usp7 deubiquitylates ubiquitylated histone H3 in vitro. Inhibition of Usp7 activity or its depletion in egg extracts results in enhanced and extended binding of Dnmt1 to chromatin, suppressing DNA Methylation. Depletion of Usp7 in HeLa cells causes enhanced histone H3 ubiquitylation and enlargement of Dnmt1 nuclear foci during DNA replication. Our results thus suggest that Usp7 is a key factor that regulates maintenance of DNA Methylation.

  • uhrf1 dependent h3k23 ubiquitylation couples maintenance DNA Methylation and replication
    Nature, 2013
    Co-Authors: Atsuya Nishiyama, Luna Yamaguchi, Yoshikazu Johmura, Kyohei Arita, Jafar Sharif, Takeshi Kawamura, Keiko Nakanishi, Shintaro Shimamura, Tatsuhiko Kodama, Fuyuki Ishikawa
    Abstract:

    The RING finger domain protein Uhrf1 is known to have an important role in DNA Methylation pattern maintenance through the recruitment of the methyltransferase Dnmt1 to hemimethylated DNA sites: here, Uhrf1 is shown to act as a ubiquitin ligase for H3, an essential step in Dnmt1 recruitment. The RING finger domain protein Uhrf1 has an essential role in maintaining patterns of DNA Methylation during replication by recruiting the DNA methyltransferase Dnmt1 to hemi-methylated DNA sites. Here, Makoto Nakanishi and colleagues reproduce maintenance DNA Methylation in an in vitro system using Xenopus egg extracts. They show that Uhrf1 is an E3 ubiquitin ligase for histone H3, and that ubiquitination of H3 is required for the recruitment of Dnmt1 to DNA replication sites. Faithful propagation of DNA Methylation patterns during DNA replication is critical for maintaining cellular phenotypes of individual differentiated cells1,2,3,4,5. Although it is well established that Uhrf1 (ubiquitin-like with PHD and ring finger domains 1; also known as Np95 and ICBP90) specifically binds to hemi-methylated DNA through its SRA (SET and RING finger associated) domain and has an essential role in maintenance of DNA Methylation by recruiting Dnmt1 to hemi-methylated DNA sites6,7,8,9,10, the mechanism by which Uhrf1 coordinates the maintenance of DNA Methylation and DNA replication is largely unknown. Here we show that Uhrf1-dependent histone H3 ubiquitylation has a prerequisite role in the maintenance DNA Methylation. Using Xenopus egg extracts, we successfully reproduce maintenance DNA Methylation in vitro. Dnmt1 depletion results in a marked accumulation of Uhrf1-dependent ubiquitylation of histone H3 at lysine 23. Dnmt1 preferentially associates with ubiquitylated H3 in vitro though a region previously identified as a replication foci targeting sequence11. The RING finger mutant of Uhrf1 fails to recruit Dnmt1 to DNA replication sites and maintain DNA Methylation in mammalian cultured cells. Our findings represent the first evidence, to our knowledge, of the mechanistic link between DNA Methylation and DNA replication through histone H3 ubiquitylation.

  • uhrf1 dependent h3k23 ubiquitylation couples maintenance DNA Methylation and replication
    Nature, 2013
    Co-Authors: Atsuya Nishiyama, Luna Yamaguchi, Yoshikazu Johmura, Kyohei Arita, Jafar Sharif, Takeshi Kawamura, Keiko Nakanishi, Shintaro Shimamura, Tatsuhiko Kodama, Fuyuki Ishikawa
    Abstract:

    Faithful propagation of DNA Methylation patterns during DNA replication is critical for maintaining cellular phenotypes of individual differentiated cells. Although it is well established that Uhrf1 (ubiquitin-like with PHD and ring finger domains 1; also known as Np95 and ICBP90) specifically binds to hemi-methylated DNA through its SRA (SET and RING finger associated) domain and has an essential role in maintenance of DNA Methylation by recruiting Dnmt1 to hemi-methylated DNA sites, the mechanism by which Uhrf1 coordinates the maintenance of DNA Methylation and DNA replication is largely unknown. Here we show that Uhrf1-dependent histone H3 ubiquitylation has a prerequisite role in the maintenance DNA Methylation. Using Xenopus egg extracts, we successfully reproduce maintenance DNA Methylation in vitro. Dnmt1 depletion results in a marked accumulation of Uhrf1-dependent ubiquitylation of histone H3 at lysine 23. Dnmt1 preferentially associates with ubiquitylated H3 in vitro though a region previously identified as a replication foci targeting sequence. The RING finger mutant of Uhrf1 fails to recruit Dnmt1 to DNA replication sites and maintain DNA Methylation in mammalian cultured cells. Our findings represent the first evidence, to our knowledge, of the mechanistic link between DNA Methylation and DNA replication through histone H3 ubiquitylation.