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Unravelling the Epigenetics of Murine Testis–Specific Histone Variants, TH2A, and TH2B in the Mature Caudal Sperm
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2022; 43(S 01): S1-S19
DOI: DOI: 10.1055/s-0042-1755518
Correspondence to: partep@nirrh.res.in
Background: Sperm-retained histones/variants are one of the most significant epigenomic contribution of father to embryo. Two such histone variants, TH2A and TH2B escape spermiogenic nuclear remodeling and are retained in the mature sperm. Importance of TH2A/TH2B in histone eviction during spermiogenesis is acknowledged. However, their significance postspermatogenesis is unknown.
Materials and Methods: Chromatin Immunoprecipitation sequencing (ChIP-seq) analysis was done to understand the epigenomics of the retained TH2B and TH2A, using murine caudal sperm.
Results: Genomic distribution revealed 35% of TH2B peaks within ±5 kb of TSS whereas TH2A was mainly intergenic. TH2B was enriched at spindle assembly and meiosis-specific genes, and embryo development was the most significant term among TH2B-associated genes (TBAGs). This is important as TH2A/TH2B DKO mice have defective cohesin release. Also, TH2A was enriched with mitochondrial function genes. Presumably, TH2A is associated with mitochondrial DNA inserted in nuclear DNA. Also, there was 26% evolutionary conservation between human and murine TBAGs including genes crucial for embryogenesis. Most importantly, heterogeneity in the epigenetic landscape of TH2A and TH2B was seen.
Conclusion: The murine TH2A/TH2B ChIP-seq analysis has attributed novel functions to sperm retained TH2B regarding embryogenesis and spermatogenesis. Conservation of TH2B-DNA linkage across two mammalian species highlights the significance of programmed histone retention for embryogenesis. Also, TH2B/TH2A is relatively independent in their epigenetic landscape. The TH2A-MtDNA link needs to be explored.
Publication History
Article published online:
22 August 2022
© 2022. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
Correspondence to: partep@nirrh.res.in
Background: Sperm-retained histones/variants are one of the most significant epigenomic contribution of father to embryo. Two such histone variants, TH2A and TH2B escape spermiogenic nuclear remodeling and are retained in the mature sperm. Importance of TH2A/TH2B in histone eviction during spermiogenesis is acknowledged. However, their significance postspermatogenesis is unknown.
Materials and Methods: Chromatin Immunoprecipitation sequencing (ChIP-seq) analysis was done to understand the epigenomics of the retained TH2B and TH2A, using murine caudal sperm.
Results: Genomic distribution revealed 35% of TH2B peaks within ±5 kb of TSS whereas TH2A was mainly intergenic. TH2B was enriched at spindle assembly and meiosis-specific genes, and embryo development was the most significant term among TH2B-associated genes (TBAGs). This is important as TH2A/TH2B DKO mice have defective cohesin release. Also, TH2A was enriched with mitochondrial function genes. Presumably, TH2A is associated with mitochondrial DNA inserted in nuclear DNA. Also, there was 26% evolutionary conservation between human and murine TBAGs including genes crucial for embryogenesis. Most importantly, heterogeneity in the epigenetic landscape of TH2A and TH2B was seen.
Conclusion: The murine TH2A/TH2B ChIP-seq analysis has attributed novel functions to sperm retained TH2B regarding embryogenesis and spermatogenesis. Conservation of TH2B-DNA linkage across two mammalian species highlights the significance of programmed histone retention for embryogenesis. Also, TH2B/TH2A is relatively independent in their epigenetic landscape. The TH2A-MtDNA link needs to be explored.
No conflict of interest has been declared by the author(s).
Publication History
Article published online:
22 August 2022
© 2022. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India