The role of histones in the maintenance of chromatin structure.

Littau, Virginia C.; Burdick, Carolyn J.; Allfrey, Vincent G.; Mirsky, S A

doi:10.1073/pnas.54.4.1204

Cited by 190 publications

(37 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since the 1960s, it has been recognised that acetylation of histones and remodelling of the tightly packed chromatin structure is associated with gene induction [4]. However, only in the last 8 yrs have the molecular mechanisms whereby inflammatory genes are switched on by transcription factors and histone acetylation become much better understood.…”

Section: Histones and Chromatin Remodellingmentioning

confidence: 99%

Histone acetylation and deacetylation: importance in inflammatory lung diseases

Barnes¹

2005

Eur Respir J

500

350

View full text Add to dashboard Cite

Inflammatory lung diseases are characterised by increased expression of multiple inflammatory genes that are regulated by proinflammatory transcription factors, such as nuclear factor-kB. Gene expression is regulated by acetylation of core histones through the action of coactivators, such as CREB-binding protein, with intrinsic histone acetyltransferase (HAT) activity.Conversely, gene repression is mediated via histone deacetylases (HDACs) and other corepressors. In asthma, there is an increase in HAT activity and some reduction in HDAC activity, which is restored by corticosteroid therapy. Corticosteroids switch off inflammatory genes in asthma through the inhibition of HAT activity and by the recruitment of HDAC2 to the activated inflammatory gene complex. In chronic obstructive pulmonary disease, there is a reduction in HDAC2 activity and expression, which may account for the amplified inflammation and resistance to the actions of corticosteroids. The reduction in HDAC2 may be secondary to oxidative and nitrative stress as a result of cigarette smoking and severe inflammation, and may also occur in severe asthma, smoking asthmatic patients and cystic fibrosis.Similar mechanisms may also account for the steroid resistance seen with latent adenovirus infections. The reduction in histone deacetylase activity can be restored by theophylline, which may be able to reverse steroid resistance in chronic obstructive pulmonary disease and other inflammatory diseases.

show abstract

Section: Histones and Chromatin Remodellingmentioning

confidence: 99%

Histone acetylation and deacetylation: importance in inflammatory lung diseases

Barnes¹

2005

Eur Respir J

500

350

View full text Add to dashboard Cite

show abstract

“…It has long been recognised that histones play a critical role in regulating the expression of genes and determine which genes are transcriptionally active and which ones are suppressed (silenced) [10]. The chromatin structure is highly organised since almost 2 m of DNA have to be packed into each cell nucleus.…”

Section: Chromatin Remodelling and Gene Expressionmentioning

confidence: 99%

Corticosteroid effects on cell signalling

Barnes¹

2006

Eur Respir J

365

245

View full text Add to dashboard Cite

Corticosteroids are the most effective anti-inflammatory therapy for asthma. Inflammation in asthma is characterised by the increased expression of multiple inflammatory genes regulated by pro-inflammatory transcription factors, such as nuclear factor-kB and activator protein-1, which bind to and activate coactivator molecules that acetylate core histones and switch on gene transcription. Corticosteroids suppress the multiple inflammatory genes that are activated in asthmatic airways, mainly by reversing histone acetylation of activated inflammatory genes through binding of glucocorticoid receptors to coactivators and recruitment of histone deacetylase 2 to the activated transcription complex.Activated glucocorticoid receptors also bind to recognition sites in the promoters of certain genes in order to activate their transcription, resulting in secretion of anti-inflammatory proteins, such as mitogen-activated protein kinase phosphatase-1, which inhibits mitogen-activated protein kinase signalling pathways. Glucocorticoid receptors may also interact with other recognition sites to inhibit transcription, for example of several genes linked to their side-effects.In some patients with steroid-resistant asthma, there are abnormalities in glucocorticoid receptor signalling pathways. In chronic obstructive pulmonary disease patients and asthmatic patients who smoke, histone deacetylase 2 is markedly impaired as a result of oxidative/nitrative stress, and so inflammation is resistant to the anti-inflammatory effects of corticosteroids.The therapeutic implications of these new findings are discussed.

show abstract

“…By either procedure, only about 7% of the extracted histone is of the lysine-rich type, and no more than a trace of nonhistone protein is removed. These selective extraction procedures have been used in this laboratory before (2,3); those involving the use of alcoholHCl were derived from a procedure of Johns et al (12).…”

mentioning

confidence: 99%

Blocking by Histones of Accessibility to DNA in Chromatin

Mirsky

Silverman

1972

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The effect of histones on accessibility of DNA to DNase in chromatin of thymus nuclei has been studied by selective extraction of either lysine-rich or arginine-rich histones. It was found that all histones block accessibility but that, weight for weight, lysine-rich histones block much more effectively than do arginine-rich histones. We point to the contrast between accessibility of DNA to DNase and of DNA to RNA polymerase, and to what may be the similarity between accessibility to DNase and DNA polymerase.DNA of chromatin in the cell nucleus is to a large extent covered with protein. This is clearly shown by use of DNase as a probe. This probe also shows that the combination between protein and DNA is loose, for as the concentration of enzyme and the time of reaction are increased, more and more DNA becomes accessible (1). We report here experiments concerning the role of histones in determining the accessibility of DNA. Lysine-rich and arginine-rich histones are compared as blockers of accessibility to DNA. Our procedure is to extract selectively either lysine-rich or argininerich histones from nuclei. Accessibility of DNA to DNase is measured before extraction and after extraction. In these experiments, we find that all histones block accessibility but that, weight for weight, lysine-rich histones block much more effectively than do arginine-rich histones.Lysine-rich histones are completely extracted from nuclei by 0.1 M citric acid; no more than traces of arginine-rich histones and other proteins are removed by this procedure. Arginine-rich histones are extracted stepwise by alcoholhydrochloric acid solutions. If HCl is held constant at 0.07 N, and the alcohol concentration is lowered from 86 to 75%, the amount of histone extracted increases; if the alcohol concentration is held constant at 80%/0, while the concentration of acid is raised from 0.03 to 0.14 N, the amount of histone extracted also increases. By either procedure, only about 7% of the extracted histone is of the lysine-rich type, and no more than a trace of nonhistone protein is removed. These selective extraction procedures have been used in this laboratory before (2, 3); those involving the use of alcoholHCl were derived from a procedure of Johns et al. (12).The effect of histone removal on the activity of DNAdependent RNA polymerases has been studied a number of times, in most cases on chromatin extracted from nuclei rather than, as in the present experiments, on chromatin in the nucleus (4-6). It is of interest to compare the accessibility of DNA in chromatin as reported from experiments on RNA polymerase with accessibility of DNA as revealed by the action of DNase. MATERIALS AND METHODSNuclei were prepared from calf thymuses which, chilled in ice, reached the laboratory within 1.5 hr after excision. Nuclei were isolated in 0.25 M sucrose-3 mM CaCI2 or in 0.01 M citric acid by methods that have been described (7,8), and were stored at -60°. The DNase used was Kunitz's preparation (9) from pancreas, as supplied by Worthington.Lysine...

show abstract

The role of histones in the maintenance of chromatin structure.

Cited by 190 publications

References 11 publications

Histone acetylation and deacetylation: importance in inflammatory lung diseases

Histone acetylation and deacetylation: importance in inflammatory lung diseases

Corticosteroid effects on cell signalling

Blocking by Histones of Accessibility to DNA in Chromatin

Contact Info

Product

Resources

About