Histone acetylation and an epigenetic code

Turner, Bryan M.

doi:10.1002/1521-1878(200009)22:9<836::aid-bies9>3.0.co;2-x

Cited by 1,066 publications

(343 citation statements)

References 65 publications

Supporting

Mentioning

326

Contrasting

Unclassified

Order By: Relevance

“…In addition, it has been proposed that a complex 'histone code' exists: specific combinations of multiple histone modifications result in the activation or repression of particular genes, thus allowing for the fine-tuning of gene expression in order to appropriately respond to a variety of environmental and nutritional cues (Jenuwein and Allis, 2001;Strahl and Allis, 2000;Turner, 2000).…”

Section: Transcriptional Repression Through Interaction Of Ogt With Sin3mentioning

confidence: 99%

Nutrient-driven O-GlcNAc cycling – think globally but act locally

Harwood

Hanover

2014

Journal of Cell Science

View full text Add to dashboard Cite

Proper cellular functioning requires that cellular machinery behave in a spatiotemporally regulated manner in response to global changes in nutrient availability. Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of Nacetylglucosamine to serine and threonine residues) and OGlcNAc turnover. Because O-GlcNAcylation levels are dependent on the nutrient-responsive hexosamine signaling pathway, this modification is uniquely poised to inform upon the nutritive state of an organism. The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. Recent reports suggest that in addition to their catalytic functions, OGT and OGA use their multifunctional domains to anchor O-GlcNAc cycling to discrete intracellular sites, thus allowing them to establish gradients of deacetylase, kinase and phosphatase signaling activities. The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. As such, the tethering of the enzymes of O-GlcNAc cycling appears to play a role in ensuring proper spatiotemporal responses to global alterations in nutrient supply.

show abstract

Section: Transcriptional Repression Through Interaction Of Ogt With Sin3mentioning

confidence: 99%

Nutrient-driven O-GlcNAc cycling – think globally but act locally

Harwood

Hanover

2014

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Of particular interest is the complement of posttranslational modifications (PTMs) that occur on histone proteins within this transcriptionally ‘off’ environment. Studies of histone PTMs such as methylation, acetylation, or phosphorylation have shown they assist in regulation of chromatin activity, which has helped usher in a modern understanding of different varieties or sub-domains of this compact chromatin state (Strahl and Allis, 2000; Turner, 2000). ‘Constitutive’ heterochromatin is found at structural or highly repetitive stretches of the genome such as pericentric or subtelomeric regions, is enriched in Su(var) (suppressors of position effect variegation) proteins and trimethylation on lysine 9 of histone H3 (H3K9me3) (James et al, 1989; Bannister et al, 2001; Jacobs et al, 2001; Peters et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Methylation of histone H3K23 blocks DNA damage in pericentric heterochromatin during meiosis

Papazyan

Voronina

Chapman

et al. 2014

eLife

View full text Add to dashboard Cite

Despite the well-established role of heterochromatin in protecting chromosomal integrity during meiosis and mitosis, the contribution and extent of heterochromatic histone posttranslational modifications (PTMs) remain poorly defined. Here, we gained novel functional insight about heterochromatic PTMs by analyzing histone H3 purified from the heterochromatic germline micronucleus of the model organism Tetrahymena thermophila. Mass spectrometric sequencing of micronuclear H3 identified H3K23 trimethylation (H3K23me3), a previously uncharacterized PTM. H3K23me3 became particularly enriched during meiotic leptotene and zygotene in germline chromatin of Tetrahymena and C. elegans. Loss of H3K23me3 in Tetrahymena through deletion of the methyltransferase Ezl3p caused mislocalization of meiosis-induced DNA double-strand breaks (DSBs) to heterochromatin, and a decrease in progeny viability. These results show that an evolutionarily conserved developmental pathway regulates H3K23me3 during meiosis, and our studies in Tetrahymena suggest this pathway may function to protect heterochromatin from DSBs.DOI: http://dx.doi.org/10.7554/eLife.02996.001

show abstract

“…Acetylation has been the most studied in cancer among all these histone modifications. Histone acetyltransferases (HATs) are responsible for the acetylation of the lysine residues of histones (Turner, 2000), while histone deacetylases (HDACs) can remove the acetyl moieties (Mottet and Castronovo, 2008; Choudhuri et al, 2010). Histones acetylation generates an open conformation of chromatin which is accessible to transcription regulators, leading to the promotion of gene expression.…”

Section: Introductionmentioning

confidence: 99%

Epigenomics of Ovarian Cancer and Its Chemoprevention

Chen¹,

Hardy²,

Tollefsbol³

2011

Front. Gene.

View full text Add to dashboard Cite

Ovarian cancer is a major cause of death among gynecological cancers and its etiology is still unclear. Currently, the two principle obstacles in treating this life threatening disease are lack of effective biomarkers for early detection and drug resistance after initial chemotherapy. Similar to other cancers, the initiation and development of ovarian cancer is characterized by disruption of oncogenes and tumor suppressor genes by both genetic and epigenetic mechanisms. While it is well known that it is challenging to treat ovarian cancer through a genetic strategy due in part to its heterogeneity, the reversibility of epigenetic mechanisms involved in ovarian cancer opens exciting new avenues for treatment. The epigenomics of ovarian cancer has therefore become a rapidly expanding field leading to intense investigation. A review on the current status of the field is thus warranted. In this analysis, we will evaluate the current status of epigenomics of ovarian cancer and will include epigenetic mechanisms involved in ovarian cancer development such as DNA methylation, histone modifications, and non-coding microRNA. Development of biomarkers, the epigenetic basis for drug resistance and improved chemotherapy for ovarian cancer will also be assessed. In addition, the potential use of natural compounds as epigenetic modulators in chemotherapy shows promise in moving to the forefront of ovarian cancer treatment strategies.

show abstract

Histone acetylation and an epigenetic code

Cited by 1,066 publications

References 65 publications

Nutrient-driven O-GlcNAc cycling – think globally but act locally

Nutrient-driven O-GlcNAc cycling – think globally but act locally

Methylation of histone H3K23 blocks DNA damage in pericentric heterochromatin during meiosis

Epigenomics of Ovarian Cancer and Its Chemoprevention

Contact Info

Product

Resources

About