Search results for "Histone code"
showing 10 items of 41 documents
Deciphering the histone code to build the genome structure
2017
Histones are punctuated with small chemical modifications that alter their interaction with DNA. One attractive hypothesis stipulates that certain combinations of these histone modifications may function, alone or together, as a part of a predictive histone code to provide ground rules for chromatin folding. We consider four features that relate histone modifications to chromatin folding: charge neutralisation, molecular specificity, robustness and evolvability. Next, we present evidence for the association among different histone modifications at various levels of chromatin organisation and show how these relationships relate to function such as transcription, replication and cell division…
Methyl-CpG-binding proteins
2000
CpG methylation, the most common epigenetic modification of vertebrate genomes, is primarily associated with transcriptional repression. MeCP2, MBD1, MBD2, MBD3 and MBD4 constitute a family of vertebrate proteins that share the methyl-CpG-binding domain (MBD). The MBD, consisting of about 70 residues, possesses a unique alpha/beta-sandwich structure with characteristic loops, and is able to bind single methylated CpG pairs as a monomer. All MBDs except MBD4, an endonuclease that forms a complex with the DNA mismatch-repair protein MLH1, form complexes with histone deacetylase. It has been established that MeCP2, MBD1 and MBD2 are involved in histone deacetylase-dependent repression and it i…
Histone Code and Higher-Order Chromatin Folding: A Hypothesis
2016
AbstractHistone modifications alone or in combination are thought to modulate chromatin structure and function; a concept termed histone code. By combining evidence from several studies, we investigated if the histone code can play a role in higher-order folding of chromatin. Firstly using genomic data, we analyzed associations between histone modifications at the nucleosome level. We could dissect the composition of individual nucleosomes into five predicted clusters of histone modifications. Secondly, by assembling the raw reads of histone modifications at various length scales, we noticed that the histone mark relationships that exist at nucleosome level tend to be maintained at the high…
Gene silencing induced by oxidative DNA base damage: association with local decrease of histone H4 acetylation in the promoter region
2010
Oxidized DNA bases, particularly 7,8-dihydro-8-oxoguanine (8-oxoG), are endogenously generated in cells, being a cause of carcinogenic mutations and possibly interfering with gene expression. We found that expression of an oxidatively damaged plasmid DNA is impaired after delivery into human host cells not only due to decreased retention in the transfected cells, but also due to selective silencing of the damaged reporter gene. To test whether the gene silencing was associated with a specific change of the chromatin structure, we determined the levels of histone modifications related to transcriptional activation (acetylated histones H3 and H4) or repression (methylated K9 and K27 of the hi…
Histone H3 Lysine 4 Mono-methylation does not Require Ubiquitination of Histone H2B
2005
The yeast Set1-complex catalyzes histone H3 lysine 4 (H3K4) methylation. Using N-terminal Edman sequencing, we determined that 50% of H3K4 is methylated and consists of roughly equal amounts of mono, di and tri-methylated H3K4. We further show that loss of either Paf1 of the Paf1 elongation complex, or ubiquitination of histone H2B, has only a modest effect on bulk histone mono-methylation at H3K4. Despite the fact that Set1 recruitment decreases in paf1delta cells, loss of Paf1 results in an increase of H3K4 mono-methylation at the 5' coding region of active genes, suggesting a Paf1-independent targeting of Set1. In contrast to Paf1 inactivation, deleting RTF1 affects H3K4 mono-methylation…
Glutathione and cellular redox control in epigenetic regulation.
2015
Epigenetics is defined as the mitotically/meiotically heritable changes in gene expression that are not due to changes in the primary DNA sequence. Over recent years, growing evidence has suggested a link between redox metabolism and the control of epigenetic mechanisms. The effect of the redox control, oxidative stress, and glutathione (GSH) on the epigenetic mechanisms occur at different levels affecting DNA methylation, miRNAs expression, and histone post-translational modifications (PTMs). Furthermore, a number of redox PTMs are being described, so enriching the histone code. Pioneer works showed how oxidized GSH inhibits the activity of S-adenosyl methionine synthetase, MAT1A, a key en…
A chromatin-associated protein from pea seeds preferentially binds histones H3 and H4
2002
Pisum sativum p16 is a protein present in the chromatin of ungerminated embryonic axes. The purification of p16 and the isolation of a cDNA clone of psp54, the gene encoding its precursor have been recently reported [Castillo, J., Rodrigo, M. I., Marquez, J. A., Zuniga, A and Franco, L. (2000) Eur. J. Biochem.267, 2156-2165]. In the present paper, we present data showing that p16 is a nuclear protein. First, after subcellular fractionation, p16 was clearly found in nuclei, although the protein is also present in other organelles. Immunocytochemical methods also confirm the above results. p16 seems to be firmly anchored to chromatin, as only extensive DNase I digestion of nuclei allows its r…
A conserved role for the mitochondrial citrate transporter Sea/SLC25A1 in the maintenance of chromosome integrity.
2009
Histone acetylation plays essential roles in cell cycle progression, DNA repair, gene expression and silencing. Although the knowledge regarding the roles of acetylation of histone lysine residues is rapidly growing, very little is known about the biochemical pathways providing the nucleus with metabolites necessary for physiological chromatin acetylation. Here, we show that mutations in the scheggia (sea)-encoded Sea protein, the Drosophila ortholog of the human mitochondrial citrate carrier Solute carrier 25 A1 (SLC25A1), impair citrate transport from mitochondria to the cytosol. Interestingly, inhibition of sea expression results in extensive chromosome breakage in mitotic cells and indu…
Histone deacetylase A key enzyme for the binding of regulatory proteins to chromatin
1993
AbstractCore histones can be modified by reversible, posttranslational acetylation of specific lysine residues within the N-terminal protein domains. The dynamic equilibrium of acetylation is maintained by two enzyme activities, histone acetyltransferase and histone deacetylase. Recent data on histone deacetylases and on anionic motifs in chromatin- or DNA-binding regulatory proteins (e.g. transcription factors, nuclear proto-oncogenes) are summarized and united into a hypothesis which attributes a key function to histone deacetylation for the binding of regulatory proteins to chromatin by a transient, specific local increase of the positive charge in the N-terminal domains of nucleosomal c…
Acetylated nucleosome assembly on telomeric DNAs
2003
Abstract The role of histone N-terminal domains on the thermodynamic stability of nucleosomes assembled on several different telomeric DNAs as well as on ‘average’ sequence DNA and on strong nucleosome positioning sequences, has been studied by competitive reconstitution. We find that histone tails hyperacetylation favors nucleosome formation, in a similar extent for all the examined sequences. On the contrary, removal of histone terminal domains by selective trypsinization causes a decrease of nucleosome stability which is smaller for telomeres compared to the other sequences examined, suggesting that telomeric sequences have only minor interactions with histone tails. Micrococcal nuclease…