Imprinted X chromosome inactivation in marsupials: The paternal X arrives at the egg with a silent DNA methylation profile
X chromosome inactivation (XCI) is an epigenetic process that results in the transcriptional silencing of one X chromosome in the somatic cells of females. This phenomenon is common to both eutherian and marsupial mammals, but there are fundamental differences. In eutherians, the X chosen for silenc...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2024-09, Vol.121 (36), p.e2412185121 |
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| creator | Milton, Ashley M Marín-Gual, Laia Lister, Nicholas C McIntyre, Kim L Grady, Patrick G S Laird, Melanie K Bond, Donna M Hore, Timothy A O'Neill, Rachel J Pask, Andrew J Renfree, Marilyn B Ruiz-Herrera, Aurora Waters, Paul D |
| description | X chromosome inactivation (XCI) is an epigenetic process that results in the transcriptional silencing of one X chromosome in the somatic cells of females. This phenomenon is common to both eutherian and marsupial mammals, but there are fundamental differences. In eutherians, the X chosen for silencing is random. DNA methylation on the eutherian inactive X is high at transcription start sites (TSSs) and their flanking regions, resulting in universally high DNA methylation. This contrasts XCI in marsupials where the paternally derived X is always silenced, and in which DNA methylation is low at TSSs and flanking regions. Here, we examined the DNA methylation status of the tammar wallaby X chromosome during spermatogenesis to determine the DNA methylation profile of the paternal X prior to and at fertilization. Whole genome enzymatic methylation sequencing was carried out on enriched flow-sorted populations of premeiotic, meiotic, and postmeiotic cells. We observed that the X displayed a pattern of DNA methylation from spermatogonia to mature sperm that reflected the inactive X in female somatic tissue. Therefore, the paternal X chromosome arrives at the egg with a DNA methylation profile that reflects the transcriptionally silent X in adult female somatic tissue. We present this epigenetic signature as a candidate for the long sought-after imprint for paternal XCI in marsupials. |
| doi_str_mv | 10.1073/pnas.2412185121 |
| format | Article |
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This phenomenon is common to both eutherian and marsupial mammals, but there are fundamental differences. In eutherians, the X chosen for silencing is random. DNA methylation on the eutherian inactive X is high at transcription start sites (TSSs) and their flanking regions, resulting in universally high DNA methylation. This contrasts XCI in marsupials where the paternally derived X is always silenced, and in which DNA methylation is low at TSSs and flanking regions. Here, we examined the DNA methylation status of the tammar wallaby X chromosome during spermatogenesis to determine the DNA methylation profile of the paternal X prior to and at fertilization. Whole genome enzymatic methylation sequencing was carried out on enriched flow-sorted populations of premeiotic, meiotic, and postmeiotic cells. We observed that the X displayed a pattern of DNA methylation from spermatogonia to mature sperm that reflected the inactive X in female somatic tissue. Therefore, the paternal X chromosome arrives at the egg with a DNA methylation profile that reflects the transcriptionally silent X in adult female somatic tissue. We present this epigenetic signature as a candidate for the long sought-after imprint for paternal XCI in marsupials.</description><identifier>ISSN: 0027-8424</identifier><identifier>ISSN: 1091-6490</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2412185121</identifier><identifier>PMID: 39190362</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Chromosomes ; Deactivation ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; DNA sequencing ; Eggs ; Epigenesis, Genetic ; Epigenetics ; Female ; Females ; Fertilization ; Gene sequencing ; Gene silencing ; Genomic Imprinting ; Inactivation ; Macropodidae - genetics ; Male ; Marsupialia - genetics ; Marsupials ; Meiosis ; Ovum - metabolism ; Somatic cells ; Spermatogenesis ; Spermatogenesis - genetics ; Spermatogonia ; Spermatozoa - metabolism ; X Chromosome - genetics ; X Chromosome Inactivation - genetics ; X chromosomes ; X-chromosome inactivation</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2024-09, Vol.121 (36), p.e2412185121</ispartof><rights>Copyright National Academy of Sciences Sep 3, 2024</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1242-adbefb66db77a975925ce104f1ff696c6944e17ccd06c3a9f52acf643bae970c3</cites><orcidid>0000-0002-4689-8747 ; 0000-0002-6735-225X ; 0000-0003-1480-0976 ; 0000-0003-3868-6151 ; 0000-0002-2847-2777 ; 0000-0002-1900-2263 ; 0000-0002-6597-4784 ; 0000-0002-4589-0436</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39190362$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Milton, Ashley M</creatorcontrib><creatorcontrib>Marín-Gual, Laia</creatorcontrib><creatorcontrib>Lister, Nicholas C</creatorcontrib><creatorcontrib>McIntyre, Kim L</creatorcontrib><creatorcontrib>Grady, Patrick G S</creatorcontrib><creatorcontrib>Laird, Melanie K</creatorcontrib><creatorcontrib>Bond, Donna M</creatorcontrib><creatorcontrib>Hore, Timothy A</creatorcontrib><creatorcontrib>O'Neill, Rachel J</creatorcontrib><creatorcontrib>Pask, Andrew J</creatorcontrib><creatorcontrib>Renfree, Marilyn B</creatorcontrib><creatorcontrib>Ruiz-Herrera, Aurora</creatorcontrib><creatorcontrib>Waters, Paul D</creatorcontrib><title>Imprinted X chromosome inactivation in marsupials: The paternal X arrives at the egg with a silent DNA methylation profile</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>X chromosome inactivation (XCI) is an epigenetic process that results in the transcriptional silencing of one X chromosome in the somatic cells of females. This phenomenon is common to both eutherian and marsupial mammals, but there are fundamental differences. In eutherians, the X chosen for silencing is random. DNA methylation on the eutherian inactive X is high at transcription start sites (TSSs) and their flanking regions, resulting in universally high DNA methylation. This contrasts XCI in marsupials where the paternally derived X is always silenced, and in which DNA methylation is low at TSSs and flanking regions. Here, we examined the DNA methylation status of the tammar wallaby X chromosome during spermatogenesis to determine the DNA methylation profile of the paternal X prior to and at fertilization. Whole genome enzymatic methylation sequencing was carried out on enriched flow-sorted populations of premeiotic, meiotic, and postmeiotic cells. We observed that the X displayed a pattern of DNA methylation from spermatogonia to mature sperm that reflected the inactive X in female somatic tissue. Therefore, the paternal X chromosome arrives at the egg with a DNA methylation profile that reflects the transcriptionally silent X in adult female somatic tissue. We present this epigenetic signature as a candidate for the long sought-after imprint for paternal XCI in marsupials.</description><subject>Animals</subject><subject>Chromosomes</subject><subject>Deactivation</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>DNA sequencing</subject><subject>Eggs</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Females</subject><subject>Fertilization</subject><subject>Gene sequencing</subject><subject>Gene silencing</subject><subject>Genomic Imprinting</subject><subject>Inactivation</subject><subject>Macropodidae - genetics</subject><subject>Male</subject><subject>Marsupialia - genetics</subject><subject>Marsupials</subject><subject>Meiosis</subject><subject>Ovum - metabolism</subject><subject>Somatic cells</subject><subject>Spermatogenesis</subject><subject>Spermatogenesis - genetics</subject><subject>Spermatogonia</subject><subject>Spermatozoa - metabolism</subject><subject>X Chromosome - genetics</subject><subject>X Chromosome Inactivation - genetics</subject><subject>X chromosomes</subject><subject>X-chromosome inactivation</subject><issn>0027-8424</issn><issn>1091-6490</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1PHDEMhqMKVBbac29VJC69zOJkMsmmN7SUFgnBZSv1NspkHDZovppkQPTXk9VSkLjYsvz4teyXkC8MlgxUeTYNJi65YJytqhw-kAUDzQopNByQBQBXxUpwcUSOY7wHAF2t4CM5KjXTUEq-IP-u-in4IWFL_1C7DWM_xrFH6gdjk38wyY9DLmhvQpwnb7r4nW62SCeTMAymy1MmBP-AkZpEU-7g3R199GlLDY2-wyHRi5tz2mPaPnV7uSmMLnc-kUOX9fDzSz4hvy9_bNa_iuvbn1fr8-vCMi54YdoGXSNl2yhltKo0rywyEI45J7W0UguBTFnbgrSl0a7ixjopysagVmDLE_Jtr5v3_p0xprr30WLXmQHHOdYlaCV0pVYyo6fv0Ptx3p2ZKQa84lXen6mzPWXDGGNAV-cX5gc91QzqnS31zpb6zZY88fVFd256bF_5_z6Uzzuyigk</recordid><startdate>20240903</startdate><enddate>20240903</enddate><creator>Milton, Ashley M</creator><creator>Marín-Gual, Laia</creator><creator>Lister, Nicholas C</creator><creator>McIntyre, Kim L</creator><creator>Grady, Patrick G S</creator><creator>Laird, Melanie K</creator><creator>Bond, Donna M</creator><creator>Hore, Timothy A</creator><creator>O'Neill, Rachel J</creator><creator>Pask, Andrew J</creator><creator>Renfree, Marilyn B</creator><creator>Ruiz-Herrera, Aurora</creator><creator>Waters, Paul D</creator><general>National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4689-8747</orcidid><orcidid>https://orcid.org/0000-0002-6735-225X</orcidid><orcidid>https://orcid.org/0000-0003-1480-0976</orcidid><orcidid>https://orcid.org/0000-0003-3868-6151</orcidid><orcidid>https://orcid.org/0000-0002-2847-2777</orcidid><orcidid>https://orcid.org/0000-0002-1900-2263</orcidid><orcidid>https://orcid.org/0000-0002-6597-4784</orcidid><orcidid>https://orcid.org/0000-0002-4589-0436</orcidid></search><sort><creationdate>20240903</creationdate><title>Imprinted X chromosome inactivation in marsupials: The paternal X arrives at the egg with a silent DNA methylation profile</title><author>Milton, Ashley M ; 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This phenomenon is common to both eutherian and marsupial mammals, but there are fundamental differences. In eutherians, the X chosen for silencing is random. DNA methylation on the eutherian inactive X is high at transcription start sites (TSSs) and their flanking regions, resulting in universally high DNA methylation. This contrasts XCI in marsupials where the paternally derived X is always silenced, and in which DNA methylation is low at TSSs and flanking regions. Here, we examined the DNA methylation status of the tammar wallaby X chromosome during spermatogenesis to determine the DNA methylation profile of the paternal X prior to and at fertilization. Whole genome enzymatic methylation sequencing was carried out on enriched flow-sorted populations of premeiotic, meiotic, and postmeiotic cells. We observed that the X displayed a pattern of DNA methylation from spermatogonia to mature sperm that reflected the inactive X in female somatic tissue. Therefore, the paternal X chromosome arrives at the egg with a DNA methylation profile that reflects the transcriptionally silent X in adult female somatic tissue. We present this epigenetic signature as a candidate for the long sought-after imprint for paternal XCI in marsupials.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>39190362</pmid><doi>10.1073/pnas.2412185121</doi><orcidid>https://orcid.org/0000-0002-4689-8747</orcidid><orcidid>https://orcid.org/0000-0002-6735-225X</orcidid><orcidid>https://orcid.org/0000-0003-1480-0976</orcidid><orcidid>https://orcid.org/0000-0003-3868-6151</orcidid><orcidid>https://orcid.org/0000-0002-2847-2777</orcidid><orcidid>https://orcid.org/0000-0002-1900-2263</orcidid><orcidid>https://orcid.org/0000-0002-6597-4784</orcidid><orcidid>https://orcid.org/0000-0002-4589-0436</orcidid></addata></record> |
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| subjects | Animals Chromosomes Deactivation Deoxyribonucleic acid DNA DNA Methylation DNA sequencing Eggs Epigenesis, Genetic Epigenetics Female Females Fertilization Gene sequencing Gene silencing Genomic Imprinting Inactivation Macropodidae - genetics Male Marsupialia - genetics Marsupials Meiosis Ovum - metabolism Somatic cells Spermatogenesis Spermatogenesis - genetics Spermatogonia Spermatozoa - metabolism X Chromosome - genetics X Chromosome Inactivation - genetics X chromosomes X-chromosome inactivation |
| title | Imprinted X chromosome inactivation in marsupials: The paternal X arrives at the egg with a silent DNA methylation profile |
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