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(The FASEB Journal. 1999;13:S216-S220.)
© 1999 FASEB

The mammalian centromere: structural domains and the attenuation of chromatin modeling

AARON A. VAN HOOSER*, MICHAEL A. MANCINI*, C. DAVID ALLIS{dagger}, KEVIN F. SULLIVAN{ddagger} and B. R. BRINKLEY1

* Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA;
{dagger} Department of Medicine, Biochemistry, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA;
{ddagger} Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA

1Correspondence: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. E-mail: brinkley{at}bcm.tmc.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 REFERENCES
 
The centromere-kinetochore complex can be divided into distinct domains based on structure and function. Previous work has used CREST auto-antibodies with various microscopic techniques to map the locations of proteins within the centromere-kinetochore complex and to analyze the maturation of prekinetochores before mitosis. Here we have focused on the centromere-specific histone Centromere Protein (CENP)-A and its spatial relationship to other histones and histone modifications found in condensed chromatin. We demonstrate that the phosphorylation of histone H3 is essentially excluded from a specific region of centromeric chromatin, defined by the presence of CENP-A. Interspersion of CENP-B with phosphorylated H3 in the inner centromere indicates that the exclusion of H3 modification is not a general property of {alpha}-satellite DNA. We also demonstrate that these regions are functionally distinct by fragmenting mitotic chromatin into motile centromere-kinetochore fragments that contain CENP-A with little or no phosphorylated H3 and nonmotile fragments that contain exclusively phosphorylated H3. The sequence of CENP-A diverges from H3 in a number of key residues involved in chromosome condensation and in transcription, potentially allowing a more specialized chromatin structure within centromeric heterochromatin, on which kinetochore plates may nucleate and mature. This specialized centromere subdomain would be predicted to have a very tight and static nucleosome structure as a result of the absence of H3 phosphorylation and acetylation.—Van Hooser, A. A., Mancini, M. A., Allis, C. D., Sullivan, K. F., Brinkley, B. R. The mammalian centromere: structural domains and the attenuation of chromatin modeling.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
REFERENCES
 
THE CENTROMERE IS best known for its function in organizing a kinetochore and modulating the attachment and movement of chromosomes on the mitotic spindle. The centromere-kinetochore complex also integrates regulatory signals required for mitotic progression and maintains sister chromatid cohesion prior to the onset of anaphase (reviewed in refs 1 , 2 ). This heterochromatin-rich locus at the primary constriction of eukaryotic chromosomes represents a novel assembly of repetitive, nontranscribing DNA and proteins, highly conserved in function, but poorly conserved in composition (reviewed in ref 3 ). In the mid-1960s, the first electron microscopic observations were made revealing a novel arrangement of the kinetochore as a trilaminar plate-like structure that clearly differentiated the kinetochore from the subjacent chromatin (4 , 5) . This distinct and transitory domain of the centromere forms at the end of prophase, functions during the ensuing stages of mitosis, and disassembles at the end of mitosis. As diagrammed in Fig. 1 , the kinetochore of mammalian chromosomes contains an outer electron dense plate with a fibrous corona visible in the absence of microtubule attachment. Separated from the outer plate by a narrow clear zone, an inner electron-dense plate can often be seen associated with the underlying centromeric chromatin.



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  		Figure 1. Domains of the centromere-kinetochore complex. The core of the centromere is formed by satellite DNA with a subset of nucleotide sequences binding kinetochore proteins (38) . CENPs-A, -C, and -G localize on and near the inner kinetochore plate (10 , 23 , 39) . Histone H3 phosphorylation is not detectable beneath the kinetochore plate and appears reduced in the pairing domain. CENP-B binds specifically to a 17-base pair motif found in some {alpha}-satellite DNA repeats and is broadly distributed in centromeric heterochromatin (40 , 41) . Facultative centromere proteins are generally associated with the outer kinetochore plate and fibrous corona (see ref 38 ).

This discovery foretold of the complex compartmentalization of the centromere that was later to be elucidated with the availability of specific auto-antibodies and the development of fluorescence microscopy using immunofluorescence and fluorescence in situ hybridization (FISH) (6) . In 1980, a group of immunologists led by Eng Tan, interested in the autoimmune aspects of rheumatoid diseases, discovered the first antibodies directed against centromere-kinetochore antigens in patients with the CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) variant of scleroderma (7) . When our laboratory and others used these valuable probes, new centromere proteins and domains were discovered, as summarized in Fig. 1 . Specifically, CREST antiserum was found to stain predominately the inner kinetochore region and recognize three constitutive centromere proteins CENPs-A, -B, and -C (8 , 9) . A fourth constitutive centromere protein, CENP-G, was recently discovered in the inner kinetochore domain using autoimmune serum from patients with watermelon-stomach disease (10) . In addition, facultative centromere proteins, such as mitotic motors and mitotic checkpoint components, have been found to localize to the outer domain of active kinetochores and regulate centromere function at discrete phases of the cell cycle (reviewed in refs 3 , 11 ).

Recent evidence suggests that the heterochromatin immediately subjacent to kinetochore plates is specialized in structure and distinct from pericentric heterochromatin and other chromosomal regions. Specifically, histone modifications appear to be markedly reduced or absent in the centromere (12 , 13) . Phosphorylation of the H3 amino-terminal tail (Ser10) initiates in the late-replicating/early-condensing heterochromatin surrounding centromeres during G2, coincident with the initiation of chromosome condensation at mammalian centromeres-prekinetochores (13 , 14) . H3 phosphorylation has spread throughout the euchromatin by prophase and is maintained until late anaphase/early telophase. However, immunoelectron microscopy reveals a lack of phosphorylated histone H3 staining within a region of the centromeric heterochromatin immediately subjacent to the kinetochore of HeLa chromosomes, whereas the pericentric heterochromatin and pairing domain stain heavily with the anti-phosphorylated H3 antibody (anti-PH3) in most sections (13) . Similarly, anti-PH3 staining does not colocalize with CREST centromere/kinetochore auto-antigens at the light microscopy level (Fig. 2 ). Using a procedure that fractionates the chromatin of cells induced to prematurely enter mitosis, CREST auto-antigens were found to occupy exclusively the centromere-kinetochore fragments that retain the capacity to capture and autonomously move along mitotic spindles (15) . Most motile centromere-kinetochore fragments contain little or no phosphorylated H3 (Fig. 3 ). As expected, H3 phosphorylation is abundant throughout the acentric, nonmotile chromosome masses. Therefore, the centromere-kinetochore represents a highly specialized region of the chromosome, both in terms of function and fundamental structure.



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  		Figure 2. A) Phosphorylated H3 appears excluded from CREST-stained centromeres-kinetochores. HeLa cells were immunostained, as described previously (6) , with CREST auto-antiserum (green) and anti-PH3 (red) (Upstate, Biotechnology, Lake Placid, N.Y.). This and all other figures are composite images obtained with a Deltavision deconvolution-based optical workstation (Applied Precision, Issaquah, Wash.). Z-series stacks of multiple focal planes were deconvolved by a constrained iterative algorithm, giving rise to high-resolution optical sections used in rendering 3-dimensional volumes. B) The same chromosome at higher magnification.



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  		Figure 3. A) CREST antigens, including CENP-A, are associated with motile centromere-kinetochore fragments, whereas phosphorylated H3 is not. Chinese hamster ovary (CHO) cells prematurely enter mitosis from the G1/S-phase boundary when treated with caffeine (15 , 42) . The chromosomes of these mitotic cells with unreplicated genomes, or MUGs, are fractured into centromere-kinetochore fragments, stained with CREST antiserum (green), which retain the capacity to attach and align on the mitotic spindle (arrows), and acentric fragments, stained with anti-PH3 (red), that do not retain the capacity for mitotic movements. B) A Z-series composite was rotated 180° around the y axis to capture two views of the same cell.

The presence of a constitutive centromere protein, CENP-A, might explain the lack of anti-PH3 reactivity within the mammalian centromere-kinetochore. CENP-A is a histone variant that copurifies with nucleosome-like particles and {alpha}-satellite DNA (16 17 18) . Though CENP-A shares homology with H3, its sequence does not contain the phosphorylated epitope (Fig. 4 ), and immunoblots exposed to the anti-PH3 antibody for prolonged periods do not cross-react with CENP-A (data not shown). An abundance of CENP-A in centromeric nucleosomes would, presumably, reduce H3 incorporation and the immunoreactivity of anti-PH3 with this region of DNA. Alternatively, a lack of H3 phosphorylation may be a result of the suppression of enzyme activity by the compact nature of heterochromatin (19) . The CREST antiserum used above (designated SH) recognizes the CENP-A antigen (20) . However, to more directly address this issue, we examined the phosphorylation of H3 in HeLa cells that express an epitope-tagged version of CENP-A (21) . CENP-A and anti-PH3 were found to occupy exclusive regions of the chromosome (Fig. 5 ). In certain human chromosomes, CREST staining spans the pairing domain, whereas CENP-A staining is consistently restricted to the kinetochore domain. Phosphorylated H3 appears reduced in the pairing domain, but not absent, suggesting that its apparent exclusion is specific to CENP-A-containing chromatin. {alpha}-satellite sequences are well known to be distributed broadly within the primary constriction and span the pairing domain of human chromosomes (Fig. 6 ). Phosphorylated H3, therefore, is not excluded from {alpha}-satellite in general. CENP-A colocalizes with only a fraction of {alpha}-satellite in human chromosomes, as shown in Fig. 7 and previously described (22 , 23) . Together, the above data suggests that the chromatin beneath the kinetochore is highly specialized in both its nucleosome composition and modification, and that the latter is not a result of the general inaccessibility of enzyme activity to regions rich in alphoid DNA.



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  		Figure 4. Phosphorylated and acetylated epitopes of the human CENP-A and histone H3 amino-terminal tails. CENP-A and H3 sequences were aligned based on homology in the carboxyl-terminal (not shown) (17) . A comparison of the NH2-terminal 30 residues indicates no homology except for a single arginine residue at position 8 and lysine residue at position 9. These residues are involved in deposition-related acetylation, carried out by B-type histone acetyltransferases (HATs) in the cytoplasm (reviewed in ref 43 ). The epitopes at which H3 is thought to be acetylated in relation to transcription (28 , 29) , catalyzed in the nucleus by A-type HATs, are not present in the CENP-A sequence. Similarly, the mitosis-specific H3 phosphorylation epitope (Ser10) is not present in the CENP-A protein.



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  		Figure 5. H3 phosphorylation appears excluded from CENP-A-chromatin, but is present in CENP-B-box-rich heterochromatin spanning the centromere. HeLa cells that express HA-tagged CENP-A were immunostained with mouse anti-HA (green) (BabCo, Richmond, Calif.), CREST antiserum (blue), and rabbit anti-PH3 (red). DNA was counterstained with DAPI (not shown).



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  		Figure 6. A) {alpha}-satellite DNA spans the pairing domain of human chromosome 1. Our method for combinatory DNA/protein staining has been given in detail (6) . An {alpha}-satellite consensus probe (red) was used to detect only the human centromeres in a hamster x human chromosome 1 hybrid cell line (arrows). The centromere-kinetochore complex of both species was stained with CREST antiserum (green). DNA was counterstained with DAPI (blue). B) A Z-series composite was rotated 180° around the y axis to capture two views of the same cell.



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  		Figure 7. CENP-A colocalizes with a small fraction of {alpha}-satellite DNA. HeLa cells expressing HA-tagged CENP-A were processed for immuno-FISH using anti-HA (green) with an {alpha}-satellite consensus probe (red). DNA was counterstained with DAPI (blue).

The phosphorylation of H3 is required for initial phases of chromosome condensation, correlating best with the folding of the ~200 nm chromatid fiber (13 , 14) . In addition, this modification may function to relax transcriptionally active chromatin with the mitogenic induction of early-response genes and make chromatin accessible to nucleases in apoptotic pathways (24 , 25) . H3 phosphorylation is not required for maintaining chromosome condensation and is therefore associated specifically with dynamic changes in chromatin structure (14 , 26) . Mechanistically, the phosphorylation of histone NH2-terminal tails has been proposed to reduce their affinity for DNA, facilitating movement of nucleosomes and targeting of trans-acting factors to the modified chromatin (13 , 25 , 27) . Lack of this epitope in the centromeric chromatin immediately subjacent to the kinetochore, as a result of the nucleosomal presence of CENP-A, might remove this chromatin from the condensation/decondensation cycle and insulate the maturing prekinetochore from dynamic changes occurring in neighboring regions of chromatin.

Similar results may be produced by the divergence of H3 acetylation epitopes in the CENP-A protein. Lysines 14 and 23 of histone H3 are preferentially acetylated in the transcriptionally active chromatin of mammalian cells, followed by acetylation of lysine 18 (28 , 29) . These three residues are not conserved in the CENP-A amino terminus (Fig. 4) . Deposition-related histone acetylation occurs in conjunction with DNA replication. Though the extent and sites may vary among diverse organisms, acetylation of H3 at lysine 9 has been associated specifically with deposition in vertebrates (reviewed in ref 30 ). In distinction from the other acetylation epitopes of H3, lysine 9 is conserved in the CENP-A amino terminus (Fig. 4) . We propose that the H3 deposition-related acetylation epitope has been conserved in the CENP-A protein to maintain fundamental aspects of nucleosome assembly, but that the transcription-related residues have diverged as a means of silencing centromeric heterochromatin.

As with phosphorylation, acetylation of histone tails is thought to weaken their association with DNA and open chromatin either directly by altering nucleosome structure (31) or indirectly by targeting nonhistone proteins (reviewed in ref 32 ). The hypoacetylation of nucleosome structure, then, would be predicted to induce a tighter conformational state of chromatin. Hypoacetylation of centromeric heterochromatin may allow a higher-order structure to develop as a necessary precursor to prekinetochore maturation (see ref 33 ). Markedly reduced levels of H3 and H4 acetylation have been observed in the centromeric heterochromatin of human chromosomes (12 , 34) . Elegant work by Allshire et al. demonstrated that in fission yeast, the inhibition of histone deacetylase activity results in a heritable disruption of centromere structure and function (35) .

The kinetochore domain is restricted to only a fraction of centromeric heterochromatin, suggesting that its nucleation and assembly may require a more highly resolved topological specification. The presence of CENP-A in the heterochromatin immediately subjacent to kinetochores may reduce the posttranslational modification of nucleosome structure in a specific region of centromeric heterochromatin, working in concert with reduced acetylase and kinase accessibility to maintain condensation constitutively and target kinetochore plate formation by providing the most suitable substratum. It seems reasonable that the genetic inactivity imposed on kinetochore-forming chromatin by both CENP-A and histone hypoacetylation may be transmitted from the centromeres of one cell generation to the next (23 , 35) . Following mitosis, the constitutive condensation of this chromatin may directly affect the temporal order of its own replication, potentially by silencing replication origins or maintaining them at low copy number (see ref 33 ). The restricted expression pattern of CENP-A in late interphase appears to target it to the late-replicating centromere (21) . Thus, hypoacetylation may maintain the greater centromere locus throughout cell division cycles, and CENP-A the kinetochore nucleation site. This model for the centromere-kinetochore cycle unites the ideas of many researchers in the field (reviewed in refs 33 , 36 , 37 ).


   ACKNOWLEDGMENTS
 
The authors thank M. G. Mancini, C. P. Schultz, and L. Zhong for technical support and B. Ledlie for secretarial assistance. This study was supported by grants from the NIH to K.F.S. (GM39068) and C.D.A. (GM40922), and from the NIH/NCI to B.R.B. (CA41424 and CA64255).


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 REFERENCES
 

  1. Gorbsky, G. J. (1997) Cell cycle checkpoints: arresting progress in mitosis. Bioessays 19,193-197[Medline]
  2. Nicklas, R. B. (1997) How cells get the right chromosomes. Science 275,632-637[Abstract/Free Full Text]
  3. Sullivan, K. F. (1998) A moveable feast: the centromere/kinetochore complex in cell division. Endow, S. Glover, D. eds. Mechanisms of Cell Division: Frontiers in Molecular Biology Oxford University Press Oxford, England.
  4. Brinkley, B. R., Stubblefield, E. (1966) The fine structure of the kinetochore of a mammalian cell in vitro. Chromosoma 19,28-43[Medline]
  5. Jokelainen, P. T. (1967) The ultrastructure and spatial organization of the metaphase kinetochore in mitotic rat cells. J. Ultrastruct. Res. 19,19-44[Medline]
  6. Van Hooser, A., Brinkley, B. R. (1999) Methods for in-situ localization of proteins and DNA in the centromere-kinetochore complex. Methods Cell Biol 61,57-80[Medline]
  7. Moroi, Y., Peebles, C., Fritzler, M., Steigerwald, J., Tan, E. (1980) Autoantibody to centromere (kinetochore) in Scleroderma sera. Proc. Natl. Acad. Sci. USA 77,1627-1631[Abstract/Free Full Text]
  8. Brenner, S., Pepper, D., Berns, M. W., Tan, E., Brinkley, B. R. (1981) Kinetochore structure, duplication, and distribution in mammalian cells: analysis by human autoantibodies from scleroderma patients. J. Cell Biol. 91,95-102[Abstract/Free Full Text]
  9. Earnshaw, W. C., Rothfield, N. F. (1985) Identification of a family of three related centromere proteins using autoimmune sera from patients with scleroderma. Chromosoma 91,313-321[Medline]
  10. He, D., Zeng, C., Woods, K., Zhong, L., Turner, D., Busch, R. K., Brinkley, B. R., Busch, H. (1998) CENP-G: a new centromeric protein that is associated with the {alpha}-1 satellite DNA subfamily. Chromosoma 107,189-197[Medline]
  11. Faulkner, N. E., Vig, B., Echeverri, C. J., Wordeman, L., Vallee, R. B. (1998) Localization of motor-related proteins and associated complexes to active, but not inactive, centromeres. Hum. Mol. Genet. 7,671-677[Abstract/Free Full Text]
  12. Jeppesen, P., Mitchell, A., Turner, B., Perry, P. (1992) Antibodies to defined histone epitopes reveal variations in chromatin conformation and underacetylation of centric heterochromatin in human metaphase chromosomes. Chromosoma 101,322-332[Medline]
  13. Hendzel, M. J., Yi, W., Mancini, M. A., Van Hooser, A., Ranalli, A., Brinkley, B. R., Bazett-Jones, D. P., Allis, C. D. (1997) Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma 106,348-360[Medline]
  14. Van Hooser, A., Goodrich, D. W., Allis, C. D., Brinkley, B. R., Mancini, M. A. (1998) Phosphorylation of histone H3 is required for the initiation, but not maintenance, of mammalian chromosome condensation. J. Cell Sci. 111,3497-3506[Abstract]
  15. Brinkley, B. R., Zinkowski, R. P., Mollon, W. L., Davis, F. M., Pisegna, M. A., Pershouse, M., Rao, P. N. (1988) Movement and segregation of kinetochores experimentally detached from mammalian chromosomes. Nature (London) 336,251-254[Medline]
  16. Palmer, D. K., O’Day, K., Werner, M. H., Andrews, B. S., Margolis, R. L. (1987) A 17 kd centromere protein (CENP-A) copurifies with nucleosome core particles and with histones. J. Cell Biol. 104,805-815[Abstract/Free Full Text]
  17. Sullivan, K. F., Hechenberger, M., Masri, K. (1994) Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere. J. Cell Biol. 127,581-592[Abstract/Free Full Text]
  18. Vafa, O., Sullivan, K. F. (1997) Chromatin containing CENP-A and {alpha}-satellite DNA is a major component of the inner kinetochore plate. Curr. Biol. 7,897-900[Medline]
  19. Thompson, J. S., Hecht, A., Grunstein, M. (1993) Histones and the regulation of heterochromatin in yeast. Cold Spring Harb. Symp. Quant. Biol. 58,247-256[Abstract/Free Full Text]
  20. Valdivia, M. M., Brinkley, B. R. (1985) Fractionation and initial characterization of the kinetochore from mammalian metaphase chromosomes. J. Cell Biol. 101,1124-1134[Abstract/Free Full Text]
  21. Shelby, R. D., Vafa, O., Sullivan, K. F. (1997) Assembly of CENP-A into centromeric chromatin requires a cooperative array of nucleosomal DNA contact sites. J. Cell Biol. 10,501-513
  22. Haaf, T., Ward, D. C. (1994) Structural analysis of {alpha}-satellite DNA and centromere proteins using extended chromatin and chromosomes. Hum. Mol. Genet. 3,697-709[Abstract/Free Full Text]
  23. Warburton, P. E., Cooke, C. A., Bourassa, S., Vafa, O., Sullivan, B. A., Stetten, G., Gimelli, G., Warburton, D., Tyler-Smith, C., Sullivan, K. F., Poirier, G. G., Earnshaw, W. C. (1997) Immunolocalization of CENP-A suggests a distinct nucleosome structure at the inner kinetochore plate of active centromeres. Curr. Biol. 7,901-904[Medline]
  24. Mahadevan, L. C., Willis, A. C., Barratt, M. J. (1991) Rapid histone H3 phosphorylation in response to growth factors, phorbol esters, okadaic acid, and protein synthesis inhibitors. Cell 65,775-783[Medline]
  25. Waring, P., Khan, T., Sjaarda, A. (1997) Apoptosis induced by gliotoxin is preceded by phosphorylation of histone H3 and enhanced sensitivity of chromatin to nuclease digestion. J. Biol. Chem. 272,17929-17936[Abstract/Free Full Text]
  26. Hanks, S. K., Rodriguez, L. V., Rao, P. N. (1983) Relationship between histone phosphorylation and premature chromosome condensation. Exp. Cell Res. 148,293-302[Medline]
  27. Roth, S. Y., Allis, C. D. (1992) Chromatin condensation: does histone H1 dephosphorylation play a role?. Trends Biol. Sci. 17,93-98
  28. Marvin, K. W., Yau, P., Bradbury, E. M. (1990) Isolation and characterization of acetylated histones H3 and H4 and their assembly into nucleosomes. J. Biol. Chem. 265,19839-19847[Abstract/Free Full Text]
  29. Thorne, A. W., Kmiciek, D., Mitchelson, K., Sautiere, P., Crane-Robinson, C. (1990) Patterns of histone acetylation. Eur. J. Biochem. 193,701-713[Medline]
  30. Mizzen, C. A., Allis, C. D. (1998) Linking histone acetylation to transcriptional regulation. Cell. Mol. Life Sci. 54,6-20[Medline]
  31. Norton, V. G., Imai, B. S., Yau, P., Bradbury, E. M. (1989) Histone acetylation reduces nucleosome core particle linking number change. Cell 57,449-457[Medline]
  32. Turner, B. M. (1998) Histone acetylation as an epigenetic determinant of long-term transcriptional competence. Cell. Mol. Life Sci. 54,21-31[Medline]
  33. Csink, A. K., Henikoff, S. (1998) Something from nothing: the evolution and utility of satellite repeats. Trends Genet 14,200-204[Medline]
  34. Belyaev, N., Keohane, A. M., Turner, B. M. (1996) Differential underacetylation of histones H2A, H3 and H4 on the inactive X chromosome in human female cells. Hum. Genet. 97,573-578[Medline]
  35. Ekwall, K., Olsson, T., Turner, B. M., Cranston, G., Allshire, R. C. (1997) Transient inhibition of histone deacetylation alters the structural and functional imprint at fission yeast centromeres. Cell 91,1021-1032[Medline]
  36. Wolffe, A. P., Pruss, D. (1996) Deviant nucleosomes: the functional specialization of chromatin. Trends Genet 12,58-62[Medline]
  37. Karpen, G. H., Allshire, R. C. (1997) The case for epigenetic effects on centromere identity and function. Trends Genet 13,489-496[Medline]
  38. Brinkley, B. R., Ouspenski, I., Zinkowski, R. P. (1992) Structure and molecular organization of the centromere-kinetochore complex. Trends Cell Biol 2,15-21
  39. Saitoh, H., Tomkiel, J., Cooke, C. A., Ratrie, H., Maurer, M., Rothfield, N. F., Earnshaw, W. C. (1992) CENP-C, an autoantigen in scleroderma, is a component of the human inner kinetochore plate. Cell 70,115-125[Medline]
  40. Masumoto, H., Masukata, H., Muro, Y., Nozaki, N., Okazaki, T. (1989) A human centromere antigen (CENP-B) interacts with a short specific sequence in alphoid DNA, a human centromeric satellite. J. Cell Biol. 109,1963-1973[Abstract/Free Full Text]
  41. Cooke, C. A., Bernat, R. B., Earnshaw, W. C. (1990) CENP-B: a major human centromere protein located beneath the kinetochore. J. Cell Biol. 110,1475-1488[Abstract/Free Full Text]
  42. Schlegel, R., Pardee, A. B. (1986) Caffeine-induced uncoupling of mitosis from the completion of DNA replication in mammalian cells. Science 232,1264-1266[Abstract/Free Full Text]
  43. Roth, S. Y., Allis, C. D. (1996) Histone acetylation and chromatin assembly: a single escort, multiple dances?. Cell 87,5-8[Medline]




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