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Encyclopedia of Physical Science and Technology EN002G-104 May 17, 2001 20:53

Chromatin Structure and Modification 829

past decade: not only is our structural understanding of 5. A number of complex events lead stalled RNA
chromatin (at least on its elementary level) more pro- polymerase to begin productive transcriptional
found than it has ever been but also a large number of elongation (which may be facilitated by
protein complexes has been discovered that are intimately hyperacetylation).
involved in transcriptional control and that can remodel
and modify chromatin structure. These developments are It is very clear that transcriptional control harbors path-
somewhat of a mixed blessing, however, because the abun- ways and mechanisms that “are not dreamt of” in our
dance of these protein factors, and our less-than-complete current paradigms. The integration of chromatin infras-
understanding of their in vivo function complicates at- tructure into gene expression regulatory pathways, how-
tempts to depict gene activation and repression as a sim- ever, is fairly certain to remain at the core of our notions
ple, linear sequence of events (e.g., “protein binds to DNA, of genome control.
protein recruits RNA polymerase, RNA polymerase syn-
thesizes mRNA”). SEE ALSO THE FOLLOWING ARTICLES
Two major questions in the field currently lack a com-
prehensive answer: (i) what are the in vivo structural con- CELL DEATH (APOPTOSIS) • GENE EXPRESSION,REGU-
sequences of chromatin remodeling and modification in LATION OF • IMMUNOLOGY-AUTOIMMUNITY • PROTEIN
terms of the behavior of the transcriptional machinery?; FOLDING • PROTEIN STRUCTURE • RIBOZYMES • TRANS-
(ii) what is the relative contribution that chromatin mod- LATION OF RNA TO PROTEIN
ification/disruption, and non-chromatin-based regulatory
pathways make to gene activation and repression in vivo? BIBLIOGRAPHY
While comprehensive answers are currently lacking, an at-
tempt at a synthesis of the current data can be made, how-
Bird, A. P., and Wolffe, A. P. (1999). “Methylation-induced repression—
ever, based on experiments on the budding yeast HO en- belts, braces, and chromatin,” Cell 99, 451–454.
donuclease gene (K. Nasmyth), MMTV LTR (G. Hager), Elgin,S.C.R.(ed.).(1995).“ChromatinStructureandGeneExpression,”
mouse serum albumin gene enhancer (K. Zaret), the Xeno- IRL Press, Oxford.
pus TRβA gene (A. Wolffe), and the Gal4-VP16 activator Grunstein, M. (1997). “Histone acetylation in chromatin structure and
transcription,” Nature 389, 349–352.
(A. Belmont). This hypothetical scenario for gene acti-
Kingston, R. E., and Narlikar, G. J. (1999). “ATP-dependent remodeling
vation is presented in the form of a numbered list, but and acetylation as regulators of chromatin fluidity,” Genes Dev. 13,
we emphasize that the sequence of some steps may be 2339–2352.
changed on specific promoters, and that some steps may Lemon, B., and Tjian, R. (2000). “Orchestrated response: A symphony
be omitted altogether. of transcription factors for gene control,” Genes Dev. 14, 2551–2569.
Luger, K., Mader, A. W., Richmond, R. K., Sargent, D. F., and Richmond,
T. J. (1997). “Crystal structure of the nucleosome core particle at 2.8
1. A transcriptional regulator accesses its binding site A resolution,” Nature 389, 251–260.
within a target promoter assembled into a mature Ng, H. H., and Bird, A. (2000). “Histone deacetylases: Silencers for
nucleosomal array. hire,” Trends Biochem Sci. 25, 121–126.
2. The chromatin-bound regulator targets an Robertson, K. R., and Wolffe, A. P. (2000). “DNA methylation in health
and disease,” Nature Rev. Genet. 1, 11–19.
ATP-dependent chromatin remodeling engine such as
Sterner, D. E., and Berger, S. L. (2000). “Acetylation of histones and
SWI/SNF; this targeting leads to the localized transcription-related factors,” Microbiol. Mol. Biol. Rev. 64, 435–459.
remodeling of the histone DNA contacts and the Struhl, K. (1998). “Histone acetylation and transcriptional regulatory
generation of a DNAse I hypersensitive site. mechanisms,” Genes Dev. 12, 599–606.
3. This remodeling allows access to the promoter of Sudarsanam, P., and Winston, F. (2000). “The Swi/Snf family:
Nucleosome-remodeling complexes and transcriptional control,”
other nonhistone factors; in concert with the “pioneer
Trends Genet. 16, 345–351.
factor,” these target HAT-containing complexes; their Urnov, F. D., and Wolffe, A. P. (2001). “A necessary food; Nuclear hor-
action may promote the large-scale unfolding of mone receptors and their chromatin templates,” Mol. Endo. 15, 1–16.
chromatin, as well as exert some local effect. Wolffe, A. P. (1998). “Chromatin Structure and Function,” Academic
4. Some of the transcriptional regulators bound to the Press, San Diego, CA.
Wolffe, A. P., and Hayes, J. J. (1999). “Chromatin disruption and modi-
promoter use other adapter complexes to promote the
fication,” Nucleic Acids Res. 27, 711–720.
assembly of the preinitiation complex and the Wolffe, A. P., and Matzke, M. A. (1999). “Epigenetics: Regulation
targeting of RNA polymerase. through repression,” Science 286, 481–486.