Loss of maternal EED results in postnatal overgrowth

Background Investigating how epigenetic information is transmitted through the mammalian germline is the key to understanding how this information impacts on health and disease susceptibility in offspring. EED is essential for regulating the repressive histone modification, histone 3 lysine 27 tri-m...
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Autor*in:	Prokopuk, Lexie [verfasserIn] Stringer, Jessica M. White, Craig R. Vossen, Rolf H. A. M. White, Stefan J. Cohen, Ana S. A. Gibson, William T. Western, Patrick S.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	Epigenetic inheritance Germ Oocyte Polycomb Histone Weaver EED EZH2 Overgrowth H3K27me3

Anmerkung:	© The Author(s). 2018

Übergeordnetes Werk:	Enthalten in: Clinical epigenetics - [S.l.] : BioMed Central, 2010, 10(2018), 1 vom: 13. Juli
Übergeordnetes Werk:	volume:10 ; year:2018 ; number:1 ; day:13 ; month:07

Links:	Volltext

DOI / URN:	10.1186/s13148-018-0526-8

Katalog-ID:	SPR030676827

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520			\|a Background Investigating how epigenetic information is transmitted through the mammalian germline is the key to understanding how this information impacts on health and disease susceptibility in offspring. EED is essential for regulating the repressive histone modification, histone 3 lysine 27 tri-methylation (H3K27me3) at many developmental genes. Results In this study, we used oocyte-specific Zp3-Cre recombinase (Zp3Cre) to delete Eed specifically in mouse growing oocytes, permitting the study of EED function in oocytes and the impact of depleting EED in oocytes on outcomes in offspring. As EED deletion occurred only in growing oocytes and females were mated to normal wild type males, this model allowed the study of oocyte programming without confounding factors such as altered in utero environment. Loss of EED from growing oocytes resulted in a significant overgrowth phenotype that persisted into adult life. Significantly, this involved increased adiposity (total fat) and bone mineral density in offspring. Similar overgrowth occurs in humans with Cohen-Gibson (OMIM 617561) and Weaver (OMIM 277590) syndromes, that result from de novo germline mutations in EED or its co-factor EZH2, respectively. Consistent with a role for EZH2 in human oocytes, we demonstrate that de novo germline mutations in EZH2 occurred in the maternal germline in some cases of Weaver syndrome. However, deletion of Ezh2 in mouse oocytes resulted in a distinct phenotype compared to that resulting from oocyte-specific deletion of Eed. Conclusions This study provides novel evidence that altering EED-dependent oocyte programming leads to compromised offspring growth and development in the next generation.
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allfields	10.1186/s13148-018-0526-8 doi (DE-627)SPR030676827 (SPR)s13148-018-0526-8-e DE-627 ger DE-627 rakwb eng Prokopuk, Lexie verfasserin aut Loss of maternal EED results in postnatal overgrowth 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2018 Background Investigating how epigenetic information is transmitted through the mammalian germline is the key to understanding how this information impacts on health and disease susceptibility in offspring. EED is essential for regulating the repressive histone modification, histone 3 lysine 27 tri-methylation (H3K27me3) at many developmental genes. Results In this study, we used oocyte-specific Zp3-Cre recombinase (Zp3Cre) to delete Eed specifically in mouse growing oocytes, permitting the study of EED function in oocytes and the impact of depleting EED in oocytes on outcomes in offspring. As EED deletion occurred only in growing oocytes and females were mated to normal wild type males, this model allowed the study of oocyte programming without confounding factors such as altered in utero environment. Loss of EED from growing oocytes resulted in a significant overgrowth phenotype that persisted into adult life. Significantly, this involved increased adiposity (total fat) and bone mineral density in offspring. Similar overgrowth occurs in humans with Cohen-Gibson (OMIM 617561) and Weaver (OMIM 277590) syndromes, that result from de novo germline mutations in EED or its co-factor EZH2, respectively. Consistent with a role for EZH2 in human oocytes, we demonstrate that de novo germline mutations in EZH2 occurred in the maternal germline in some cases of Weaver syndrome. However, deletion of Ezh2 in mouse oocytes resulted in a distinct phenotype compared to that resulting from oocyte-specific deletion of Eed. Conclusions This study provides novel evidence that altering EED-dependent oocyte programming leads to compromised offspring growth and development in the next generation. Epigenetic inheritance (dpeaa)DE-He213 Germ (dpeaa)DE-He213 Oocyte (dpeaa)DE-He213 Polycomb (dpeaa)DE-He213 Histone (dpeaa)DE-He213 Weaver (dpeaa)DE-He213 EED (dpeaa)DE-He213 EZH2 (dpeaa)DE-He213 Overgrowth (dpeaa)DE-He213 H3K27me3 (dpeaa)DE-He213 Stringer, Jessica M. aut White, Craig R. aut Vossen, Rolf H. A. M. aut White, Stefan J. aut Cohen, Ana S. A. aut Gibson, William T. aut Western, Patrick S. (orcid)0000-0002-7587-8227 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 10(2018), 1 vom: 13. Juli (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:10 year:2018 number:1 day:13 month:07 https://dx.doi.org/10.1186/s13148-018-0526-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2018 1 13 07
spelling	10.1186/s13148-018-0526-8 doi (DE-627)SPR030676827 (SPR)s13148-018-0526-8-e DE-627 ger DE-627 rakwb eng Prokopuk, Lexie verfasserin aut Loss of maternal EED results in postnatal overgrowth 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2018 Background Investigating how epigenetic information is transmitted through the mammalian germline is the key to understanding how this information impacts on health and disease susceptibility in offspring. EED is essential for regulating the repressive histone modification, histone 3 lysine 27 tri-methylation (H3K27me3) at many developmental genes. Results In this study, we used oocyte-specific Zp3-Cre recombinase (Zp3Cre) to delete Eed specifically in mouse growing oocytes, permitting the study of EED function in oocytes and the impact of depleting EED in oocytes on outcomes in offspring. As EED deletion occurred only in growing oocytes and females were mated to normal wild type males, this model allowed the study of oocyte programming without confounding factors such as altered in utero environment. Loss of EED from growing oocytes resulted in a significant overgrowth phenotype that persisted into adult life. Significantly, this involved increased adiposity (total fat) and bone mineral density in offspring. Similar overgrowth occurs in humans with Cohen-Gibson (OMIM 617561) and Weaver (OMIM 277590) syndromes, that result from de novo germline mutations in EED or its co-factor EZH2, respectively. Consistent with a role for EZH2 in human oocytes, we demonstrate that de novo germline mutations in EZH2 occurred in the maternal germline in some cases of Weaver syndrome. However, deletion of Ezh2 in mouse oocytes resulted in a distinct phenotype compared to that resulting from oocyte-specific deletion of Eed. Conclusions This study provides novel evidence that altering EED-dependent oocyte programming leads to compromised offspring growth and development in the next generation. Epigenetic inheritance (dpeaa)DE-He213 Germ (dpeaa)DE-He213 Oocyte (dpeaa)DE-He213 Polycomb (dpeaa)DE-He213 Histone (dpeaa)DE-He213 Weaver (dpeaa)DE-He213 EED (dpeaa)DE-He213 EZH2 (dpeaa)DE-He213 Overgrowth (dpeaa)DE-He213 H3K27me3 (dpeaa)DE-He213 Stringer, Jessica M. aut White, Craig R. aut Vossen, Rolf H. A. M. aut White, Stefan J. aut Cohen, Ana S. A. aut Gibson, William T. aut Western, Patrick S. (orcid)0000-0002-7587-8227 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 10(2018), 1 vom: 13. Juli (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:10 year:2018 number:1 day:13 month:07 https://dx.doi.org/10.1186/s13148-018-0526-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2018 1 13 07
allfields_unstemmed	10.1186/s13148-018-0526-8 doi (DE-627)SPR030676827 (SPR)s13148-018-0526-8-e DE-627 ger DE-627 rakwb eng Prokopuk, Lexie verfasserin aut Loss of maternal EED results in postnatal overgrowth 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2018 Background Investigating how epigenetic information is transmitted through the mammalian germline is the key to understanding how this information impacts on health and disease susceptibility in offspring. EED is essential for regulating the repressive histone modification, histone 3 lysine 27 tri-methylation (H3K27me3) at many developmental genes. Results In this study, we used oocyte-specific Zp3-Cre recombinase (Zp3Cre) to delete Eed specifically in mouse growing oocytes, permitting the study of EED function in oocytes and the impact of depleting EED in oocytes on outcomes in offspring. As EED deletion occurred only in growing oocytes and females were mated to normal wild type males, this model allowed the study of oocyte programming without confounding factors such as altered in utero environment. Loss of EED from growing oocytes resulted in a significant overgrowth phenotype that persisted into adult life. Significantly, this involved increased adiposity (total fat) and bone mineral density in offspring. Similar overgrowth occurs in humans with Cohen-Gibson (OMIM 617561) and Weaver (OMIM 277590) syndromes, that result from de novo germline mutations in EED or its co-factor EZH2, respectively. Consistent with a role for EZH2 in human oocytes, we demonstrate that de novo germline mutations in EZH2 occurred in the maternal germline in some cases of Weaver syndrome. However, deletion of Ezh2 in mouse oocytes resulted in a distinct phenotype compared to that resulting from oocyte-specific deletion of Eed. Conclusions This study provides novel evidence that altering EED-dependent oocyte programming leads to compromised offspring growth and development in the next generation. Epigenetic inheritance (dpeaa)DE-He213 Germ (dpeaa)DE-He213 Oocyte (dpeaa)DE-He213 Polycomb (dpeaa)DE-He213 Histone (dpeaa)DE-He213 Weaver (dpeaa)DE-He213 EED (dpeaa)DE-He213 EZH2 (dpeaa)DE-He213 Overgrowth (dpeaa)DE-He213 H3K27me3 (dpeaa)DE-He213 Stringer, Jessica M. aut White, Craig R. aut Vossen, Rolf H. A. M. aut White, Stefan J. aut Cohen, Ana S. A. aut Gibson, William T. aut Western, Patrick S. (orcid)0000-0002-7587-8227 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 10(2018), 1 vom: 13. Juli (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:10 year:2018 number:1 day:13 month:07 https://dx.doi.org/10.1186/s13148-018-0526-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2018 1 13 07
allfieldsGer	10.1186/s13148-018-0526-8 doi (DE-627)SPR030676827 (SPR)s13148-018-0526-8-e DE-627 ger DE-627 rakwb eng Prokopuk, Lexie verfasserin aut Loss of maternal EED results in postnatal overgrowth 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2018 Background Investigating how epigenetic information is transmitted through the mammalian germline is the key to understanding how this information impacts on health and disease susceptibility in offspring. EED is essential for regulating the repressive histone modification, histone 3 lysine 27 tri-methylation (H3K27me3) at many developmental genes. Results In this study, we used oocyte-specific Zp3-Cre recombinase (Zp3Cre) to delete Eed specifically in mouse growing oocytes, permitting the study of EED function in oocytes and the impact of depleting EED in oocytes on outcomes in offspring. As EED deletion occurred only in growing oocytes and females were mated to normal wild type males, this model allowed the study of oocyte programming without confounding factors such as altered in utero environment. Loss of EED from growing oocytes resulted in a significant overgrowth phenotype that persisted into adult life. Significantly, this involved increased adiposity (total fat) and bone mineral density in offspring. Similar overgrowth occurs in humans with Cohen-Gibson (OMIM 617561) and Weaver (OMIM 277590) syndromes, that result from de novo germline mutations in EED or its co-factor EZH2, respectively. Consistent with a role for EZH2 in human oocytes, we demonstrate that de novo germline mutations in EZH2 occurred in the maternal germline in some cases of Weaver syndrome. However, deletion of Ezh2 in mouse oocytes resulted in a distinct phenotype compared to that resulting from oocyte-specific deletion of Eed. Conclusions This study provides novel evidence that altering EED-dependent oocyte programming leads to compromised offspring growth and development in the next generation. Epigenetic inheritance (dpeaa)DE-He213 Germ (dpeaa)DE-He213 Oocyte (dpeaa)DE-He213 Polycomb (dpeaa)DE-He213 Histone (dpeaa)DE-He213 Weaver (dpeaa)DE-He213 EED (dpeaa)DE-He213 EZH2 (dpeaa)DE-He213 Overgrowth (dpeaa)DE-He213 H3K27me3 (dpeaa)DE-He213 Stringer, Jessica M. aut White, Craig R. aut Vossen, Rolf H. A. M. aut White, Stefan J. aut Cohen, Ana S. A. aut Gibson, William T. aut Western, Patrick S. (orcid)0000-0002-7587-8227 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 10(2018), 1 vom: 13. Juli (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:10 year:2018 number:1 day:13 month:07 https://dx.doi.org/10.1186/s13148-018-0526-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2018 1 13 07
allfieldsSound	10.1186/s13148-018-0526-8 doi (DE-627)SPR030676827 (SPR)s13148-018-0526-8-e DE-627 ger DE-627 rakwb eng Prokopuk, Lexie verfasserin aut Loss of maternal EED results in postnatal overgrowth 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2018 Background Investigating how epigenetic information is transmitted through the mammalian germline is the key to understanding how this information impacts on health and disease susceptibility in offspring. EED is essential for regulating the repressive histone modification, histone 3 lysine 27 tri-methylation (H3K27me3) at many developmental genes. Results In this study, we used oocyte-specific Zp3-Cre recombinase (Zp3Cre) to delete Eed specifically in mouse growing oocytes, permitting the study of EED function in oocytes and the impact of depleting EED in oocytes on outcomes in offspring. As EED deletion occurred only in growing oocytes and females were mated to normal wild type males, this model allowed the study of oocyte programming without confounding factors such as altered in utero environment. Loss of EED from growing oocytes resulted in a significant overgrowth phenotype that persisted into adult life. Significantly, this involved increased adiposity (total fat) and bone mineral density in offspring. Similar overgrowth occurs in humans with Cohen-Gibson (OMIM 617561) and Weaver (OMIM 277590) syndromes, that result from de novo germline mutations in EED or its co-factor EZH2, respectively. Consistent with a role for EZH2 in human oocytes, we demonstrate that de novo germline mutations in EZH2 occurred in the maternal germline in some cases of Weaver syndrome. However, deletion of Ezh2 in mouse oocytes resulted in a distinct phenotype compared to that resulting from oocyte-specific deletion of Eed. Conclusions This study provides novel evidence that altering EED-dependent oocyte programming leads to compromised offspring growth and development in the next generation. Epigenetic inheritance (dpeaa)DE-He213 Germ (dpeaa)DE-He213 Oocyte (dpeaa)DE-He213 Polycomb (dpeaa)DE-He213 Histone (dpeaa)DE-He213 Weaver (dpeaa)DE-He213 EED (dpeaa)DE-He213 EZH2 (dpeaa)DE-He213 Overgrowth (dpeaa)DE-He213 H3K27me3 (dpeaa)DE-He213 Stringer, Jessica M. aut White, Craig R. aut Vossen, Rolf H. A. M. aut White, Stefan J. aut Cohen, Ana S. A. aut Gibson, William T. aut Western, Patrick S. (orcid)0000-0002-7587-8227 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 10(2018), 1 vom: 13. Juli (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:10 year:2018 number:1 day:13 month:07 https://dx.doi.org/10.1186/s13148-018-0526-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2018 1 13 07
language	English
source	Enthalten in Clinical epigenetics 10(2018), 1 vom: 13. Juli volume:10 year:2018 number:1 day:13 month:07
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spellingShingle	Prokopuk, Lexie misc Epigenetic inheritance misc Germ misc Oocyte misc Polycomb misc Histone misc Weaver misc EED misc EZH2 misc Overgrowth misc H3K27me3 Loss of maternal EED results in postnatal overgrowth
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topic_title	Loss of maternal EED results in postnatal overgrowth Epigenetic inheritance (dpeaa)DE-He213 Germ (dpeaa)DE-He213 Oocyte (dpeaa)DE-He213 Polycomb (dpeaa)DE-He213 Histone (dpeaa)DE-He213 Weaver (dpeaa)DE-He213 EED (dpeaa)DE-He213 EZH2 (dpeaa)DE-He213 Overgrowth (dpeaa)DE-He213 H3K27me3 (dpeaa)DE-He213
topic	misc Epigenetic inheritance misc Germ misc Oocyte misc Polycomb misc Histone misc Weaver misc EED misc EZH2 misc Overgrowth misc H3K27me3
topic_unstemmed	misc Epigenetic inheritance misc Germ misc Oocyte misc Polycomb misc Histone misc Weaver misc EED misc EZH2 misc Overgrowth misc H3K27me3
topic_browse	misc Epigenetic inheritance misc Germ misc Oocyte misc Polycomb misc Histone misc Weaver misc EED misc EZH2 misc Overgrowth misc H3K27me3
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title	Loss of maternal EED results in postnatal overgrowth
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title_sort	loss of maternal eed results in postnatal overgrowth
title_auth	Loss of maternal EED results in postnatal overgrowth
abstract	Background Investigating how epigenetic information is transmitted through the mammalian germline is the key to understanding how this information impacts on health and disease susceptibility in offspring. EED is essential for regulating the repressive histone modification, histone 3 lysine 27 tri-methylation (H3K27me3) at many developmental genes. Results In this study, we used oocyte-specific Zp3-Cre recombinase (Zp3Cre) to delete Eed specifically in mouse growing oocytes, permitting the study of EED function in oocytes and the impact of depleting EED in oocytes on outcomes in offspring. As EED deletion occurred only in growing oocytes and females were mated to normal wild type males, this model allowed the study of oocyte programming without confounding factors such as altered in utero environment. Loss of EED from growing oocytes resulted in a significant overgrowth phenotype that persisted into adult life. Significantly, this involved increased adiposity (total fat) and bone mineral density in offspring. Similar overgrowth occurs in humans with Cohen-Gibson (OMIM 617561) and Weaver (OMIM 277590) syndromes, that result from de novo germline mutations in EED or its co-factor EZH2, respectively. Consistent with a role for EZH2 in human oocytes, we demonstrate that de novo germline mutations in EZH2 occurred in the maternal germline in some cases of Weaver syndrome. However, deletion of Ezh2 in mouse oocytes resulted in a distinct phenotype compared to that resulting from oocyte-specific deletion of Eed. Conclusions This study provides novel evidence that altering EED-dependent oocyte programming leads to compromised offspring growth and development in the next generation. © The Author(s). 2018
abstractGer	Background Investigating how epigenetic information is transmitted through the mammalian germline is the key to understanding how this information impacts on health and disease susceptibility in offspring. EED is essential for regulating the repressive histone modification, histone 3 lysine 27 tri-methylation (H3K27me3) at many developmental genes. Results In this study, we used oocyte-specific Zp3-Cre recombinase (Zp3Cre) to delete Eed specifically in mouse growing oocytes, permitting the study of EED function in oocytes and the impact of depleting EED in oocytes on outcomes in offspring. As EED deletion occurred only in growing oocytes and females were mated to normal wild type males, this model allowed the study of oocyte programming without confounding factors such as altered in utero environment. Loss of EED from growing oocytes resulted in a significant overgrowth phenotype that persisted into adult life. Significantly, this involved increased adiposity (total fat) and bone mineral density in offspring. Similar overgrowth occurs in humans with Cohen-Gibson (OMIM 617561) and Weaver (OMIM 277590) syndromes, that result from de novo germline mutations in EED or its co-factor EZH2, respectively. Consistent with a role for EZH2 in human oocytes, we demonstrate that de novo germline mutations in EZH2 occurred in the maternal germline in some cases of Weaver syndrome. However, deletion of Ezh2 in mouse oocytes resulted in a distinct phenotype compared to that resulting from oocyte-specific deletion of Eed. Conclusions This study provides novel evidence that altering EED-dependent oocyte programming leads to compromised offspring growth and development in the next generation. © The Author(s). 2018
abstract_unstemmed	Background Investigating how epigenetic information is transmitted through the mammalian germline is the key to understanding how this information impacts on health and disease susceptibility in offspring. EED is essential for regulating the repressive histone modification, histone 3 lysine 27 tri-methylation (H3K27me3) at many developmental genes. Results In this study, we used oocyte-specific Zp3-Cre recombinase (Zp3Cre) to delete Eed specifically in mouse growing oocytes, permitting the study of EED function in oocytes and the impact of depleting EED in oocytes on outcomes in offspring. As EED deletion occurred only in growing oocytes and females were mated to normal wild type males, this model allowed the study of oocyte programming without confounding factors such as altered in utero environment. Loss of EED from growing oocytes resulted in a significant overgrowth phenotype that persisted into adult life. Significantly, this involved increased adiposity (total fat) and bone mineral density in offspring. Similar overgrowth occurs in humans with Cohen-Gibson (OMIM 617561) and Weaver (OMIM 277590) syndromes, that result from de novo germline mutations in EED or its co-factor EZH2, respectively. Consistent with a role for EZH2 in human oocytes, we demonstrate that de novo germline mutations in EZH2 occurred in the maternal germline in some cases of Weaver syndrome. However, deletion of Ezh2 in mouse oocytes resulted in a distinct phenotype compared to that resulting from oocyte-specific deletion of Eed. Conclusions This study provides novel evidence that altering EED-dependent oocyte programming leads to compromised offspring growth and development in the next generation. © The Author(s). 2018
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fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR030676827</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519071100.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2018 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s13148-018-0526-8</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR030676827</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s13148-018-0526-8-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Prokopuk, Lexie</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Loss of maternal EED results in postnatal overgrowth</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2018</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s). 2018</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Investigating how epigenetic information is transmitted through the mammalian germline is the key to understanding how this information impacts on health and disease susceptibility in offspring. EED is essential for regulating the repressive histone modification, histone 3 lysine 27 tri-methylation (H3K27me3) at many developmental genes. Results In this study, we used oocyte-specific Zp3-Cre recombinase (Zp3Cre) to delete Eed specifically in mouse growing oocytes, permitting the study of EED function in oocytes and the impact of depleting EED in oocytes on outcomes in offspring. As EED deletion occurred only in growing oocytes and females were mated to normal wild type males, this model allowed the study of oocyte programming without confounding factors such as altered in utero environment. Loss of EED from growing oocytes resulted in a significant overgrowth phenotype that persisted into adult life. Significantly, this involved increased adiposity (total fat) and bone mineral density in offspring. Similar overgrowth occurs in humans with Cohen-Gibson (OMIM 617561) and Weaver (OMIM 277590) syndromes, that result from de novo germline mutations in EED or its co-factor EZH2, respectively. Consistent with a role for EZH2 in human oocytes, we demonstrate that de novo germline mutations in EZH2 occurred in the maternal germline in some cases of Weaver syndrome. However, deletion of Ezh2 in mouse oocytes resulted in a distinct phenotype compared to that resulting from oocyte-specific deletion of Eed. 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Loss of maternal EED results in postnatal overgrowth

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