Epigenetic Mechanisms
Permanent URI for this community
During human development a single zygote differentiates into approximately 200 different cell types that, despite being genetically identical, maintain their cellular identity through mitotic divisions. Therefore, in addition to the genomic information embedded in the primary DNA sequence, epigenetic information is propagated as well, that “memorizes” gene activity states and specific chromatin structures across somatic division and sometimes even across generations.
Browse
Browsing Epigenetic Mechanisms by Author "Black, B. E."
Now showing 1 - 3 of 3
Results Per Page
Sort Options
- Assembly in G1 phase and long-term stability are unique intrinsic features of CENP-A nucleosomesPublication . Bodor, D. L.; Valente, L. P.; Mata, J. F.; Black, B. E.; Jansen, L. E. T.Centromeres are the site of kinetochore formation during mitosis. Centromere protein A (CENP-A), the centromere-specific histone H3 variant, is essential for the epigenetic maintenance of centromere position. Previously we showed that newly synthesized CENP-A is targeted to centromeres exclusively during early G1 phase and is subsequently maintained across mitotic divisions. Using SNAP-based fluorescent pulse labeling, we now demonstrate that cell cycle-restricted chromatin assembly at centromeres is unique to CENP-A nucleosomes and does not involve assembly of other H3 variants. Strikingly, stable retention is restricted to the CENP-A/H4 core of the nucleosome, which we find to outlast general chromatin across several cell divisions. We further show that cell cycle timing of CENP-A assembly is independent of centromeric DNA sequences and instead is mediated by the CENP-A targeting domain. Unexpectedly, this domain also induces stable transmission of centromeric nucleosomes, independent of the CENP-A deposition factor HJURP. This demonstrates that intrinsic properties of the CENP-A protein direct its cell cycle-restricted assembly and induces quantitative mitotic transmission of the CENP-A/H4 nucleosome core, ensuring long-term stability and epigenetic maintenance of centromere position.
- Chromosomes. CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromerePublication . Falk, S. J.; Guo, L. Y.; Sekulic, N.; Smoak, E. M.; Mani, T.; Logsdon, G. A.; Gupta, K.; Jansen, L. E. T.; Van Duyne, G. D.; Vinogradov, S. A.; Lampson, M. A.; Black, B. E.Inheritance of each chromosome depends upon its centromere. A histone H3 variant, centromere protein A (CENP-A), is essential for epigenetically marking centromere location. We find that CENP-A is quantitatively retained at the centromere upon which it is initially assembled. CENP-C binds to CENP-A nucleosomes and is a prime candidate to stabilize centromeric chromatin. Using purified components, we find that CENP-C reshapes the octameric histone core of CENP-A nucleosomes, rigidifies both surface and internal nucleosome structure, and modulates terminal DNA to match the loose wrap that is found on native CENP-A nucleosomes at functional human centromeres. Thus, CENP-C affects nucleosome shape and dynamics in a manner analogous to allosteric regulation of enzymes. CENP-C depletion leads to rapid removal of CENP-A from centromeres, indicating their collaboration in maintaining centromere identity.
- Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variantPublication . Earnshaw, W. C.; Allshire, R. C.; Black, B. E.; Bloom, K.; Brinkley, B. R.; Brown, W.; Cheeseman, I. M.; Choo, K. H. A.; Copenhaver, G. P.; DeLuca, J. G.; Desai, A.; Diekmann, S.; Erhardt, S.; Fitzgerald-Hayes, M.; Foltz, D.; Fukagawa, T.; Gassmann, R.; Gerlich, D. W.; Glover, D. M.; Gorbsky, G. J.; Harrison, S. C.; Heun, P.; Hirota, T.; Jansen, L. E. T.; Karpen, G.; Kops, G. J. P. L.; Lampson, M. A.; Lens, S. M.; Losada, A.; Luger, K.; Maiato, H.; Maddox, P. S.; Margolis, R. L.; Masumoto, H.; McAinsh, A. D.; Mellone, B. G.; Meraldi, P.; Musacchio, A.; Oegema, K.; O’Neill, R. J.; Salmon, E. D.; Scott, K. C.; Straight, A. F.; Stukenberg, P. T.; Sullivan, B. A.; Sullivan, K. F.; Sunkel, C. E.; Swedlow, J. R.; Walczak, C. E.; Warburton, P. E.; Westermann, S.; Willard, H. F.; Wordeman, L.; Yanagida, M.; Yen, T. J.; Yoda, K.; Cleveland, D. W.The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres.