Chromatin Remodelling and Histone Modification in Transcription Regulation


The eukaryotic genome is assembled into chromatin, localized alterations of which are a major feature of gene control pathways. A wide variety of dedicated enzymatic complexes are targeted by particular transcriptional regulators to specific loci in the genome and remodel the structure of chromatin via energy‐dependent disruption of histone–DNA contacts and covalent modification of histones, both with major regulatory consequences.

Keywords: transcription; nucleosome; chromatin remodelling; histone deacetylase; histone acetyltransferase

Figure 1.

Mapping DNAse I‐hypersensitive sites in chromatin using indirect end labelling. This technique was developed in 1980 by S. Nedospasov and G. Georgiev, and independently by C. Wu and S. Elgin. The outline of the experiment is shown on the left: nuclei are isolated from tissue culture cells or tissue, treated briefly with DNAse I, the DNA is extracted and digested to completion with a restriction endonuclease. Sites of cleavage by DNAse I in chromatin are revealed by Southern blotting with a probe that abuts one end of a chosen restriction fragment. An example of the data generated by this approach is shown on the right: the gene shown changes activity during development, and thus one can examine chromatin structure at various developmental stages. Pronounced cleavage by DNAse I (red arrowheads) is only observed at the transcription start site and at a stretch of regulatory DNA located about 500 bp upstream only when the gene is active. The ‘end’ lane shows that the tissue used contains endogenous nucleases that will also preferentially cleave chromatin within the DNAse I‐hypersensitive sites, if longer incubation times are used. The model system used here is the fly Sciara (see Gerbi SA, Liang N, Wu N et al., Cold Spring Harbor Symposia of Quantitative Biology58: 487).

Figure 2.

A schematic of the core histone octamer (centre) with the DNA superhelix (blue) and the core histone tails extended to their full length. Lysine residues that can be modified by acetylation are indicated with an asterisk. From Wolffe AP and Hayes J Nucleic Acids Research27: 711. Copyright 1999 Oxford University Press. Used by permission.

Figure 3.

Revealing the binding sites of specific proteins in chromatin by chromatin immunoprecipitation (ChIP). This technique was developed in 1988 by M. Solomon and A. Varshavsky and subsequently (in 1991) by M. Gorovsky and D. Allis. The outline of the experiment is shown on the left: cells are briefly treated with formaldehyde to introduce covalent crosslinks between proteins and DNA. Chromatin is isolated and sheared into small (<1‐kb) fragments, followed by an immunoprecipitation against a protein of interest (ellipse). The crosslinks are then eliminated, protein removed, and the DNA analysed by polymerase chain reaction for the presence of specific sequences. An example of such data is shown on the right. The upper right panel shows that the yeast HDAC Rpd3p is required for the transcriptional repression of the INO1 gene (second panel) – this Northern blot demonstrates that INO1 levels are low in wild‐type cells, but increase dramatically if the RPD3 gene is inactivated (‘rpd3’ lane). A ChIP experiment on the INO1 locus with an antibody against hyperacetylated histones is shown on the lower right: the top line is the map of the gene, and the bottom data set is a PCR reaction performed with multiple primer pairs (these detect fragments over the entire locus). Compared with the input lanes (on the right), only a fragment over the transcription start site (‘–0.09 kb’) is not immunoprecipitated with this antibody (second lane). When the RPD3 gene is inactivated (‘rpd3’), acetylation over that stretch of DNA becomes equal to that seen over adjacent areas. Thus, transcriptional repression by Rpd3p of the INO1 gene (top right) occurs concomitant with a deacetylation of chromatin over its transcription start site (bottom right). From Rundlett SE, Carmen A, Suka N et al. (1998) Nature392: 831. Copyright 1998 Macmillan Publishers.

Figure 4.

Histone tail acetylation affects the functional and structural properties of chromatin. The panel on the left shows a transcription assay performed with hyperacetylated (‘H’) and unacetylated (‘U’) chromatin. Massive amounts of read‐through transcripts are generated on the former, but not the latter template (left panel). The top right panel shows a schematic representation of shape changes that chromatin undergoes in solutions of various ionic strength. The lower right panel shows that altering the acetylation state of chromatin (‘H’ stands for ‘hyperacetylated’ and ‘M’ for ‘moderately acetylated’) changes its folding: hyperacetylated fibres are more unfolded (extended) and thus have a lower Svedberg number. From Tse C, Sera T, Wolffe AP et al. (1988) Molecular and Cellular Biology18: 4629. Copyright 1988 American Society for Microbiology. Used by permission.

Figure 5.

A hypermethylated promoter is silenced via the targeting of histone deacetylase. From Robertson KR and Wolffe AP Nature Reviews Genetics1: 11. Copyright 2000 Macmillan Publishers.



Allfrey V, Faulkner RM and Mirsky AE (1964) Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proceedings of the National Academy of Sciences of the USA 51: 786–794.

Archer TK, Lefebvre P, Wolford RG and Hager GL (1992) Transcription factor loading on the MMTV promoter: a bimodal mechanism for promoter activation. Science 255: 1573–1576.

Brownell JE, Zhou J, Ranalli T et al. (1996) Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84: 843–851.

Clever U and Karlson P (1960) Induktion von Puff‐Veraenderungen in den Speicheldruesenchromosomen von Chironomus tentans durch Ecdyson. Experimental Cell Research 20: 623–626.

Cosma MP, Tanaka T and Nasmyth K (1999) Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle‐ and developmentally regulated promoter. Cell 97: 299–311.

Gross DS and Garrard WT (1988) Nuclease hypersensitive sites in chromatin. Annual Review of Biochemistry 57: 159–197.

Hebbes TR, Thorne AW and Crane‐Robinson C (1988) A direct link between core histone acetylation and transcriptionally active chromatin. EMBO Journal 7: 1395–1402.

Hebbes TR, Clayton AL, Thorne AW and Crane‐Robinson C (1994) Core histone hyperacetylation co‐maps with generalized DNase I sensitivity in the chicken β‐globin chromosomal domain. EMBO Journal 13: 1823–1830.

Heitz E (1928) Das Heterochromatin der Moose. Jahrbuch Wissenschaftlichen Botanik 69: 762.

Hewish DR and Burgoyne LA (1973) Chromatin sub‐structure. The digestion of chromatin DNA at regularly spaced sites by a nuclear deoxyribonuclease. Biochemical Biophysical Research Communications 52: 504–510.

Hirschhorn JN, Brown SA, Clark CD and Winston F (1992) Evidence that SNF2/SWI2 and SNF5 activate transcription in yeast by altering chromatin structure. Genes and Development 6: 2288–2298.

Kingston RE and Narlikar GJ (1999) ATP‐dependent remodeling and acetylation as regulators of chromatin fluidity. Genes and Development 13: 2339–23352.

Kornberg RD and Thomas JO (1974) Chromatin structure; oligomers of the histones. Science 184: 865–886.

Lemon B and Tjian R (2000) Orchestrated response: a symphony of transcription factors for gene control. Genes and Development 14: 2551–2569.

Lyon MF (1961) Gene action in the X‐chromosome of the mouse. Nature 190: 372–373.

McNally JG, Muller WG, Walker D, Wolford R and Hager GL (2000) The glucocorticoid receptor: rapid exchange with regulatory sites in living cells. Science 287: 1262–1265.

Nedospasov S and Georgiev G (1980) Non‐random cleavage of SV40 DNA in the compact minichromosome and free in solution by micrococcal nuclease. Biochemical Biophysical Research Communications 29: 532–539.

Ng HH and Bird A (2000) Histone deacetylases: silencers for hire. Trends in Biochemical Science 25: 121–126.

Ohno S, Kaplan WD and Kinosita R (1959) Formation of the sex chromatin by a single X‐chromosome in liver cells of Rattus norvegicus. Experimental Cell Research 18: 415–418.

Robertson KR and Wolffe AP (2000) DNA methylation in health and disease. Nature Reviews Genetics 1: 11–19.

Sterner DE and Berger SL (2000) Acetylation of histones and transcription‐related factors. Microbiology and Molecular Biology Reviews 64: 435–459.

Sudarsanam P and Winston F (2000) The Swi/Snf family: nucleosome‐remodeling complexes and transcriptional control. Trends in Genetics 16: 345–351.

Taunton J, Hassig CA and Schreiber SL (1996) A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 272: 408–411.

Urnov FD and Wolffe AP (2001) A necessary good: nuclear hormone receptors and their chromatin templates. Molecular Endocrinology 15: 1–16.

Wolffe AP (1998) Chromatin Structure and Function. San Diego, CA: Academic Press.

Wolffe AP and Guschin D (2000) Chromatin structural features and targets that regulate transcription. Journal of Structural Biology 129: 102–122.

Wolffe AP and Hayes JJ (1999) Chromatin disruption and modification. Nucleic Acids Research 27: 711–720.

Wu C (1980) The 5′ ends of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature 286: 854–860.

Young RA (2000) Biomedical discovery with DNA arrays. Cell 102: 9–15.

Zaret KS and Yamamoto KR (1984) Reversible and persistent changes in chromatin structure accompany activation of a glucocorticoid‐dependent enhancer element. Cell 38: 29–38.

Zhang W, Bone JR, Edmondson DG, Turner BM and Roth SY (1998) Essential and redundant functions of histone acetylation revealed by mutation of target lysines and loss of the Gcn5p acetyltransferase. EMBO Journal 17: 3155–3167.

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Urnov, Fyodor D, and Wolffe, Alan P(Jul 2001) Chromatin Remodelling and Histone Modification in Transcription Regulation. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0003304]