The Sequence Dependent Nanoscale Structure of CENP-A Nucleosomes
CENP-A is a histone variant found in high abundance at the centromere in humans. At the centromere, this histone variant replaces the histone H3 found throughout the bulk chromatin. Additionally, the centromere comprises tandem repeats of α-satellite DNA, which CENP-A nucleosomes assemble upon. Howe...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/19/11385 |
| _version_ | 1797479079224541184 |
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| author | Tommy Stormberg Yuri L. Lyubchenko |
| author_facet | Tommy Stormberg Yuri L. Lyubchenko |
| author_sort | Tommy Stormberg |
| collection | DOAJ |
| description | CENP-A is a histone variant found in high abundance at the centromere in humans. At the centromere, this histone variant replaces the histone H3 found throughout the bulk chromatin. Additionally, the centromere comprises tandem repeats of α-satellite DNA, which CENP-A nucleosomes assemble upon. However, the effect of the DNA sequence on the nucleosome assembly and centromere formation remains poorly understood. Here, we investigated the structure of nucleosomes assembled with the CENP-A variant using Atomic Force Microscopy. We assembled both CENP-A nucleosomes and H3 nucleosomes on a DNA substrate containing an α-satellite motif and characterized their positioning and wrapping efficiency. We also studied CENP-A nucleosomes on the 601-positioning motif and non-specific DNA to compare their relative positioning and stability. CENP-A nucleosomes assembled on α-satellite DNA did not show any positional preference along the substrate, which is similar to both H3 nucleosomes and CENP-A nucleosomes on non-specific DNA. The range of nucleosome wrapping efficiency was narrower on α-satellite DNA compared with non-specific DNA, suggesting a more stable complex. These findings indicate that DNA sequence and histone composition may be two of many factors required for accurate centromere assembly. |
| first_indexed | 2024-03-09T21:40:42Z |
| format | Article |
| id | doaj.art-ead54ceb514b4d18924206a1dd83b1d4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:40:42Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ead54ceb514b4d18924206a1dd83b1d42023-11-23T20:32:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123191138510.3390/ijms231911385The Sequence Dependent Nanoscale Structure of CENP-A NucleosomesTommy Stormberg0Yuri L. Lyubchenko1Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USACENP-A is a histone variant found in high abundance at the centromere in humans. At the centromere, this histone variant replaces the histone H3 found throughout the bulk chromatin. Additionally, the centromere comprises tandem repeats of α-satellite DNA, which CENP-A nucleosomes assemble upon. However, the effect of the DNA sequence on the nucleosome assembly and centromere formation remains poorly understood. Here, we investigated the structure of nucleosomes assembled with the CENP-A variant using Atomic Force Microscopy. We assembled both CENP-A nucleosomes and H3 nucleosomes on a DNA substrate containing an α-satellite motif and characterized their positioning and wrapping efficiency. We also studied CENP-A nucleosomes on the 601-positioning motif and non-specific DNA to compare their relative positioning and stability. CENP-A nucleosomes assembled on α-satellite DNA did not show any positional preference along the substrate, which is similar to both H3 nucleosomes and CENP-A nucleosomes on non-specific DNA. The range of nucleosome wrapping efficiency was narrower on α-satellite DNA compared with non-specific DNA, suggesting a more stable complex. These findings indicate that DNA sequence and histone composition may be two of many factors required for accurate centromere assembly.https://www.mdpi.com/1422-0067/23/19/11385centromere chromatinCENP-A nucleosomesatomic force microscopynanoscale structure of nucleosomesalpha satellite DNA |
| spellingShingle | Tommy Stormberg Yuri L. Lyubchenko The Sequence Dependent Nanoscale Structure of CENP-A Nucleosomes International Journal of Molecular Sciences centromere chromatin CENP-A nucleosomes atomic force microscopy nanoscale structure of nucleosomes alpha satellite DNA |
| title | The Sequence Dependent Nanoscale Structure of CENP-A Nucleosomes |
| title_full | The Sequence Dependent Nanoscale Structure of CENP-A Nucleosomes |
| title_fullStr | The Sequence Dependent Nanoscale Structure of CENP-A Nucleosomes |
| title_full_unstemmed | The Sequence Dependent Nanoscale Structure of CENP-A Nucleosomes |
| title_short | The Sequence Dependent Nanoscale Structure of CENP-A Nucleosomes |
| title_sort | sequence dependent nanoscale structure of cenp a nucleosomes |
| topic | centromere chromatin CENP-A nucleosomes atomic force microscopy nanoscale structure of nucleosomes alpha satellite DNA |
| url | https://www.mdpi.com/1422-0067/23/19/11385 |
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