Human-specific epigenomic states in spermatogenesis
Infertility is becoming increasingly common, affecting one in six people globally. Half of these cases can be attributed to male factors, many driven by abnormalities in the process of sperm development. Emerging evidence from genome-wide association studies, genetic screening of patient cohorts, an...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037023005123 |
| _version_ | 1797364200779022336 |
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| author | Caiyun Liao Benjamin William Walters Marcello DiStasio Bluma J. Lesch |
| author_facet | Caiyun Liao Benjamin William Walters Marcello DiStasio Bluma J. Lesch |
| author_sort | Caiyun Liao |
| collection | DOAJ |
| description | Infertility is becoming increasingly common, affecting one in six people globally. Half of these cases can be attributed to male factors, many driven by abnormalities in the process of sperm development. Emerging evidence from genome-wide association studies, genetic screening of patient cohorts, and animal models highlights an important genetic contribution to spermatogenic defects, but comprehensive identification and characterization of the genes critical for male fertility remain lacking. High divergence of gene regulation in spermatogenic cells across species poses challenges for delineating the genetic pathways required for human spermatogenesis using common model organisms. In this study, we leveraged post-translational histone modification and gene transcription data for 15,491 genes in four mammalian species (human, rhesus macaque, mouse, and opossum), to identify human-specific patterns of gene regulation during spermatogenesis. We combined H3K27me3 ChIP-seq, H3K4me3 ChIP-seq, and RNA-seq data to define epigenetic states for each gene at two stages of spermatogenesis, pachytene spermatocytes and round spermatids, in each species. We identified 239 genes that are uniquely active, poised, or dynamically regulated in human spermatogenic cells distinct from the other three species. While some of these genes have been implicated in reproductive functions, many more have not yet been associated with human infertility and may be candidates for further molecular and epidemiologic studies. Our analysis offers an example of the opportunities provided by evolutionary and epigenomic data for broadly screening candidate genes implicated in reproduction, which might lead to discoveries of novel genetic targets for diagnosis and management of male infertility and male contraception. |
| first_indexed | 2024-03-08T16:31:48Z |
| format | Article |
| id | doaj.art-069007c9878d4b53a2e5d56173b0dd02 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T16:31:48Z |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-069007c9878d4b53a2e5d56173b0dd022024-01-06T04:38:44ZengElsevierComputational and Structural Biotechnology Journal2001-03702024-12-0123577588Human-specific epigenomic states in spermatogenesisCaiyun Liao0Benjamin William Walters1Marcello DiStasio2Bluma J. Lesch3Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, 333 Cedar St., New Haven, CT 06510, USADepartment of Genetics, Yale School of Medicine, 333 Cedar St., New Haven, CT 06510, USADepartment of Pathology, Yale School of Medicine, 333 Cedar St., New Haven, CT 06510, USA; Department of Opthamology & Visual Sciences, Yale School of Medicine, 333 Cedar St., New Haven, CT 06510, USADepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, 333 Cedar St., New Haven, CT 06510, USA; Department of Genetics, Yale School of Medicine, 333 Cedar St., New Haven, CT 06510, USA; Yale Cancer Center, Yale School of Medicine, 333 Cedar St., New Haven, CT 06510, USA; Correspondence to: 333 Cedar St., New Haven, CT 06510, USA.Infertility is becoming increasingly common, affecting one in six people globally. Half of these cases can be attributed to male factors, many driven by abnormalities in the process of sperm development. Emerging evidence from genome-wide association studies, genetic screening of patient cohorts, and animal models highlights an important genetic contribution to spermatogenic defects, but comprehensive identification and characterization of the genes critical for male fertility remain lacking. High divergence of gene regulation in spermatogenic cells across species poses challenges for delineating the genetic pathways required for human spermatogenesis using common model organisms. In this study, we leveraged post-translational histone modification and gene transcription data for 15,491 genes in four mammalian species (human, rhesus macaque, mouse, and opossum), to identify human-specific patterns of gene regulation during spermatogenesis. We combined H3K27me3 ChIP-seq, H3K4me3 ChIP-seq, and RNA-seq data to define epigenetic states for each gene at two stages of spermatogenesis, pachytene spermatocytes and round spermatids, in each species. We identified 239 genes that are uniquely active, poised, or dynamically regulated in human spermatogenic cells distinct from the other three species. While some of these genes have been implicated in reproductive functions, many more have not yet been associated with human infertility and may be candidates for further molecular and epidemiologic studies. Our analysis offers an example of the opportunities provided by evolutionary and epigenomic data for broadly screening candidate genes implicated in reproduction, which might lead to discoveries of novel genetic targets for diagnosis and management of male infertility and male contraception.http://www.sciencedirect.com/science/article/pii/S2001037023005123ExpressionHistone modificationGenomicsFertilitySpermatogenesisEvolution |
| spellingShingle | Caiyun Liao Benjamin William Walters Marcello DiStasio Bluma J. Lesch Human-specific epigenomic states in spermatogenesis Computational and Structural Biotechnology Journal Expression Histone modification Genomics Fertility Spermatogenesis Evolution |
| title | Human-specific epigenomic states in spermatogenesis |
| title_full | Human-specific epigenomic states in spermatogenesis |
| title_fullStr | Human-specific epigenomic states in spermatogenesis |
| title_full_unstemmed | Human-specific epigenomic states in spermatogenesis |
| title_short | Human-specific epigenomic states in spermatogenesis |
| title_sort | human specific epigenomic states in spermatogenesis |
| topic | Expression Histone modification Genomics Fertility Spermatogenesis Evolution |
| url | http://www.sciencedirect.com/science/article/pii/S2001037023005123 |
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