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5 results on '"Allshire RC"'

1. C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line

Author

Zoch, A, Konieczny, G, Auchynnikava, T, Stallmeyer, B, Rotte, N, Heep, M, Berrens, RV, Schito, M, Kabayama, Y, Schopp, T, Kliesch, S, Houston, B, Nagirnaja, L, O'Bryan, MK, Aston, KI, Conrad, DF, Rappsilber, J, Allshire, RC, Cook, AG, Tuettelmann, F, O'Carroll, D, Zoch, A, Konieczny, G, Auchynnikava, T, Stallmeyer, B, Rotte, N, Heep, M, Berrens, RV, Schito, M, Kabayama, Y, Schopp, T, Kliesch, S, Houston, B, Nagirnaja, L, O'Bryan, MK, Aston, KI, Conrad, DF, Rappsilber, J, Allshire, RC, Cook, AG, Tuettelmann, F, and O'Carroll, D

Abstract

In the male mouse germ line, PIWI-interacting RNAs (piRNAs), bound by the PIWI protein MIWI2 (PIWIL4), guide DNA methylation of young active transposons through SPOCD1. However, the underlying mechanisms of SPOCD1-mediated piRNA-directed transposon methylation and whether this pathway functions to protect the human germ line remain unknown. We identified loss-of-function variants in human SPOCD1 that cause defective transposon silencing and male infertility. Through the analysis of these pathogenic alleles, we discovered that the uncharacterized protein C19ORF84 interacts with SPOCD1. DNMT3C, the DNA methyltransferase responsible for transposon methylation, associates with SPOCD1 and C19ORF84 in fetal gonocytes. Furthermore, C19ORF84 is essential for piRNA-directed DNA methylation and male mouse fertility. Finally, C19ORF84 mediates the in vivo association of SPOCD1 with the de novo methylation machinery. In summary, we have discovered a conserved role for the human piRNA pathway in transposon silencing and C19ORF84, an uncharacterized protein essential for orchestrating piRNA-directed DNA methylation.

Published
2024

2. The RFTS Domain of Raf2 Is Required for Cul4 Interaction and Heterochromatin Integrity in Fission Yeast.

Author

White, SA, Buscaino, Alessia, Sanchez-Pulido, L, Ponting, CP, Nowicki, MW, Allshire, RC, White, SA, Buscaino, Alessia, Sanchez-Pulido, L, Ponting, CP, Nowicki, MW, and Allshire, RC

Abstract

Centromeric heterochromatin assembly in fission yeast is critical for faithful chromosome segregation at mitosis. Its assembly requires a concerted pathway of events whereby the RNA interference (RNAi) pathway guides H3K9 methylation to target sequences. H3K9 methylation, a hallmark of heterochromatin structure, is mediated by the single histone methyltransferase Clr4 (equivalent to metazoan Suv3-9), a component of the CLRC complex. Loss of or defects in CLRC components disrupts heterochromatin formation due to loss of H3K9 methylation, thus an intact, fully functional CLRC complex is required for heterochromatin integrity. Despite its importance, little is known about the contribution of the CLRC component Raf2 to H3K9 methylation and heterochromatin assembly. We demonstrate that Raf2 is concentrated at centromeres and contrary to other analyses, we find that loss of Raf2 does not affect CENP-ACnp1 localisation or recruitment to centromeres. Our sequence alignments show that Raf2 contains a Replication Foci Targeting Sequence (RFTS) domain homologous to the RFTS domain of the human DNA methyltransferase DNMT1. We show that the Raf2 RFTS domain is required for centromeric heterochromatin formation as its mutation disrupts H3K9 methylation but not the processing of centromeric transcripts into small interfering RNAs (siRNAs) by the RNAi pathway. Analysis of biochemical interactions demonstrates that the RFTS domain mediates an interaction between Raf2 and the CLRC component Cul4. We conclude that the RFTS domain of Raf2 is a protein interaction module that plays an important role in heterochromatin formation at centromeres.

Published
2014

3. Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant.

Author

Earnshaw, WC, Earnshaw, WC, Allshire, RC, Black, BE, Bloom, K, Brinkley, BR, Brown, W, Cheeseman, IM, Choo, KHA, Copenhaver, GP, Deluca, JG, Desai, A, Diekmann, S, Erhardt, S, Fitzgerald-Hayes, M, Foltz, D, Fukagawa, T, Gassmann, R, Gerlich, DW, Glover, DM, Gorbsky, GJ, Harrison, SC, Heun, P, Hirota, T, Jansen, LET, Karpen, G, Kops, GJPL, Lampson, MA, Lens, SM, Losada, A, Luger, K, Maiato, H, Maddox, PS, Margolis, RL, Masumoto, H, McAinsh, AD, Mellone, BG, Meraldi, P, Musacchio, A, Oegema, K, O'Neill, RJ, Salmon, ED, Scott, KC, Straight, AF, Stukenberg, PT, Sullivan, BA, Sullivan, KF, Sunkel, CE, Swedlow, JR, Walczak, CE, Warburton, PE, Westermann, S, Willard, HF, Wordeman, L, Yanagida, M, Yen, TJ, Yoda, K, Cleveland, DW, Earnshaw, WC, Earnshaw, WC, Allshire, RC, Black, BE, Bloom, K, Brinkley, BR, Brown, W, Cheeseman, IM, Choo, KHA, Copenhaver, GP, Deluca, JG, Desai, A, Diekmann, S, Erhardt, S, Fitzgerald-Hayes, M, Foltz, D, Fukagawa, T, Gassmann, R, Gerlich, DW, Glover, DM, Gorbsky, GJ, Harrison, SC, Heun, P, Hirota, T, Jansen, LET, Karpen, G, Kops, GJPL, Lampson, MA, Lens, SM, Losada, A, Luger, K, Maiato, H, Maddox, PS, Margolis, RL, Masumoto, H, McAinsh, AD, Mellone, BG, Meraldi, P, Musacchio, A, Oegema, K, O'Neill, RJ, Salmon, ED, Scott, KC, Straight, AF, Stukenberg, PT, Sullivan, BA, Sullivan, KF, Sunkel, CE, Swedlow, JR, Walczak, CE, Warburton, PE, Westermann, S, Willard, HF, Wordeman, L, Yanagida, M, Yen, TJ, Yoda, K, and Cleveland, DW

Abstract

The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres.

Published
2013

4. Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant

Author

Earnshaw, WC, Allshire, RC, Black, BE, Bloom, K, Brinkley, BR, Brown, W, Cheeseman, IM, Choo, KHA, Copenhaver, GP, DeLuca, JG, Desai, A, Diekmann, S, Erhardt, S, Fitzgerald-Hayes, M, Foltz, D, Fukagawa, T, Gassmann, R, Gerlich, DW, Glover, DM, Gorbsky, GJ, Harrison, SC, Heun, P, Hirota, T, Jansen, LET, Karpen, G, Kops, GJPL, Lampson, MA, Lens, SM, Losada, A, Luger, K, Maiato, H, Maddox, PS, Margolis, RL, Masumoto, H, McAinsh, AD, Mellone, BG, Meraldi, P, Musacchio, A, Oegema, K, O'Neill, RJ, Salmon, ED, Scott, KC, Straight, AF, Stukenberg, PT, Sullivan, BA, Sullivan, KF, Sunkel, CE, Swedlow, JR, Walczak, CE, Warburton, PE, Westermann, S, Willard, HF, Wordeman, L, Yanagida, M, Yen, TJ, Yoda, K, Cleveland, DW, Earnshaw, WC, Allshire, RC, Black, BE, Bloom, K, Brinkley, BR, Brown, W, Cheeseman, IM, Choo, KHA, Copenhaver, GP, DeLuca, JG, Desai, A, Diekmann, S, Erhardt, S, Fitzgerald-Hayes, M, Foltz, D, Fukagawa, T, Gassmann, R, Gerlich, DW, Glover, DM, Gorbsky, GJ, Harrison, SC, Heun, P, Hirota, T, Jansen, LET, Karpen, G, Kops, GJPL, Lampson, MA, Lens, SM, Losada, A, Luger, K, Maiato, H, Maddox, PS, Margolis, RL, Masumoto, H, McAinsh, AD, Mellone, BG, Meraldi, P, Musacchio, A, Oegema, K, O'Neill, RJ, Salmon, ED, Scott, KC, Straight, AF, Stukenberg, PT, Sullivan, BA, Sullivan, KF, Sunkel, CE, Swedlow, JR, Walczak, CE, Warburton, PE, Westermann, S, Willard, HF, Wordeman, L, Yanagida, M, Yen, TJ, Yoda, K, and Cleveland, DW

Abstract

The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres.

Published
2013

5. Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant.

Author

Earnshaw, WC, Earnshaw, WC, Allshire, RC, Black, BE, Bloom, K, Brinkley, BR, Brown, W, Cheeseman, IM, Choo, KHA, Copenhaver, GP, Deluca, JG, Desai, A, Diekmann, S, Erhardt, S, Fitzgerald-Hayes, M, Foltz, D, Fukagawa, T, Gassmann, R, Gerlich, DW, Glover, DM, Gorbsky, GJ, Harrison, SC, Heun, P, Hirota, T, Jansen, LET, Karpen, G, Kops, GJPL, Lampson, MA, Lens, SM, Losada, A, Luger, K, Maiato, H, Maddox, PS, Margolis, RL, Masumoto, H, McAinsh, AD, Mellone, BG, Meraldi, P, Musacchio, A, Oegema, K, O'Neill, RJ, Salmon, ED, Scott, KC, Straight, AF, Stukenberg, PT, Sullivan, BA, Sullivan, KF, Sunkel, CE, Swedlow, JR, Walczak, CE, Warburton, PE, Westermann, S, Willard, HF, Wordeman, L, Yanagida, M, Yen, TJ, Yoda, K, Cleveland, DW, Earnshaw, WC, Earnshaw, WC, Allshire, RC, Black, BE, Bloom, K, Brinkley, BR, Brown, W, Cheeseman, IM, Choo, KHA, Copenhaver, GP, Deluca, JG, Desai, A, Diekmann, S, Erhardt, S, Fitzgerald-Hayes, M, Foltz, D, Fukagawa, T, Gassmann, R, Gerlich, DW, Glover, DM, Gorbsky, GJ, Harrison, SC, Heun, P, Hirota, T, Jansen, LET, Karpen, G, Kops, GJPL, Lampson, MA, Lens, SM, Losada, A, Luger, K, Maiato, H, Maddox, PS, Margolis, RL, Masumoto, H, McAinsh, AD, Mellone, BG, Meraldi, P, Musacchio, A, Oegema, K, O'Neill, RJ, Salmon, ED, Scott, KC, Straight, AF, Stukenberg, PT, Sullivan, BA, Sullivan, KF, Sunkel, CE, Swedlow, JR, Walczak, CE, Warburton, PE, Westermann, S, Willard, HF, Wordeman, L, Yanagida, M, Yen, TJ, Yoda, K, and Cleveland, DW

Abstract

The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres.

Published
2013

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