RNA-Guided Genomic Localization of H2A.L.2 Histone Variant
The molecular basis of residual histone retention after the nearly genome-wide histone-to-protamine replacement during late spermatogenesis is a critical and open question. Our previous investigations showed that in postmeiotic male germ cells, the genome-scale incorporation of histone variants TH2B...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-02-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/9/2/474 |
| _version_ | 1797714169740394496 |
|---|---|
| author | Naghmeh Hoghoughi Sophie Barral Sandrine Curtet Florent Chuffart Guillaume Charbonnier Denis Puthier Thierry Buchou Sophie Rousseaux Saadi Khochbin |
| author_facet | Naghmeh Hoghoughi Sophie Barral Sandrine Curtet Florent Chuffart Guillaume Charbonnier Denis Puthier Thierry Buchou Sophie Rousseaux Saadi Khochbin |
| author_sort | Naghmeh Hoghoughi |
| collection | DOAJ |
| description | The molecular basis of residual histone retention after the nearly genome-wide histone-to-protamine replacement during late spermatogenesis is a critical and open question. Our previous investigations showed that in postmeiotic male germ cells, the genome-scale incorporation of histone variants TH2B-H2A.L.2 allows a controlled replacement of histones by protamines to occur. Here, we highlight the intrinsic ability of H2A.L.2 to specifically target the pericentric regions of the genome and discuss why pericentric heterochromatin is a privileged site of histone retention in mature spermatozoa. We observed that the intranuclear localization of H2A.L.2 is controlled by its ability to bind RNA, as well as by an interplay between its RNA-binding activity and its tropism for pericentric heterochromatin. We identify the H2A.L.2 RNA-binding domain and demonstrate that in somatic cells, the replacement of H2A.L.2 RNA-binding motif enhances and stabilizes its pericentric localization, while the forced expression of RNA increases its homogenous nuclear distribution. Based on these data, we propose that the specific accumulation of RNA on pericentric regions combined with H2A.L.2 tropism for these regions are responsible for stabilizing H2A.L.2 on these regions in mature spermatozoa. This situation would favor histone retention on pericentric heterochromatin. |
| first_indexed | 2024-03-12T07:47:57Z |
| format | Article |
| id | doaj.art-921561e156414732a71468dcd3afe11a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:47:57Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-921561e156414732a71468dcd3afe11a2023-09-02T20:52:43ZengMDPI AGCells2073-44092020-02-019247410.3390/cells9020474cells9020474RNA-Guided Genomic Localization of H2A.L.2 Histone VariantNaghmeh Hoghoughi0Sophie Barral1Sandrine Curtet2Florent Chuffart3Guillaume Charbonnier4Denis Puthier5Thierry Buchou6Sophie Rousseaux7Saadi Khochbin8CNRS UMR 5309; Inserm, U1209; Université Grenoble Alpes; Institute for Advanced Biosciences, F- 38700 Grenoble, FranceCNRS UMR 5309; Inserm, U1209; Université Grenoble Alpes; Institute for Advanced Biosciences, F- 38700 Grenoble, FranceCNRS UMR 5309; Inserm, U1209; Université Grenoble Alpes; Institute for Advanced Biosciences, F- 38700 Grenoble, FranceCNRS UMR 5309; Inserm, U1209; Université Grenoble Alpes; Institute for Advanced Biosciences, F- 38700 Grenoble, FranceTGML, platform IbiSA; Aix Marseille Univ, Inserm U1090, TAGC, 13288 Marseille, FranceTGML, platform IbiSA; Aix Marseille Univ, Inserm U1090, TAGC, 13288 Marseille, FranceCNRS UMR 5309; Inserm, U1209; Université Grenoble Alpes; Institute for Advanced Biosciences, F- 38700 Grenoble, FranceCNRS UMR 5309; Inserm, U1209; Université Grenoble Alpes; Institute for Advanced Biosciences, F- 38700 Grenoble, FranceCNRS UMR 5309; Inserm, U1209; Université Grenoble Alpes; Institute for Advanced Biosciences, F- 38700 Grenoble, FranceThe molecular basis of residual histone retention after the nearly genome-wide histone-to-protamine replacement during late spermatogenesis is a critical and open question. Our previous investigations showed that in postmeiotic male germ cells, the genome-scale incorporation of histone variants TH2B-H2A.L.2 allows a controlled replacement of histones by protamines to occur. Here, we highlight the intrinsic ability of H2A.L.2 to specifically target the pericentric regions of the genome and discuss why pericentric heterochromatin is a privileged site of histone retention in mature spermatozoa. We observed that the intranuclear localization of H2A.L.2 is controlled by its ability to bind RNA, as well as by an interplay between its RNA-binding activity and its tropism for pericentric heterochromatin. We identify the H2A.L.2 RNA-binding domain and demonstrate that in somatic cells, the replacement of H2A.L.2 RNA-binding motif enhances and stabilizes its pericentric localization, while the forced expression of RNA increases its homogenous nuclear distribution. Based on these data, we propose that the specific accumulation of RNA on pericentric regions combined with H2A.L.2 tropism for these regions are responsible for stabilizing H2A.L.2 on these regions in mature spermatozoa. This situation would favor histone retention on pericentric heterochromatin.https://www.mdpi.com/2073-4409/9/2/474histone dynamicstestis-specific histone variantsepigenetic inheritancerepetitive elementscentromere |
| spellingShingle | Naghmeh Hoghoughi Sophie Barral Sandrine Curtet Florent Chuffart Guillaume Charbonnier Denis Puthier Thierry Buchou Sophie Rousseaux Saadi Khochbin RNA-Guided Genomic Localization of H2A.L.2 Histone Variant Cells histone dynamics testis-specific histone variants epigenetic inheritance repetitive elements centromere |
| title | RNA-Guided Genomic Localization of H2A.L.2 Histone Variant |
| title_full | RNA-Guided Genomic Localization of H2A.L.2 Histone Variant |
| title_fullStr | RNA-Guided Genomic Localization of H2A.L.2 Histone Variant |
| title_full_unstemmed | RNA-Guided Genomic Localization of H2A.L.2 Histone Variant |
| title_short | RNA-Guided Genomic Localization of H2A.L.2 Histone Variant |
| title_sort | rna guided genomic localization of h2a l 2 histone variant |
| topic | histone dynamics testis-specific histone variants epigenetic inheritance repetitive elements centromere |
| url | https://www.mdpi.com/2073-4409/9/2/474 |
| work_keys_str_mv | AT naghmehhoghoughi rnaguidedgenomiclocalizationofh2al2histonevariant AT sophiebarral rnaguidedgenomiclocalizationofh2al2histonevariant AT sandrinecurtet rnaguidedgenomiclocalizationofh2al2histonevariant AT florentchuffart rnaguidedgenomiclocalizationofh2al2histonevariant AT guillaumecharbonnier rnaguidedgenomiclocalizationofh2al2histonevariant AT denisputhier rnaguidedgenomiclocalizationofh2al2histonevariant AT thierrybuchou rnaguidedgenomiclocalizationofh2al2histonevariant AT sophierousseaux rnaguidedgenomiclocalizationofh2al2histonevariant AT saadikhochbin rnaguidedgenomiclocalizationofh2al2histonevariant |