Archive for the ‘Epigenetics’ Category
Monday, May 14th, 2012
Epigenetic alterations have come to prominence in biomedical research. In particular, hypermethylation of CpG islands located in the promoter regions of tumor-suppressor genes is now firmly established as an important mechanism for gene inactivation in cancer. Polycomb group (PcG) proteins are epigenetic chromatin modifiers involved in gene silencing, cancer development and the maintenance of adult and embryonic stem cells. One of the most remarkable achievements in the field has also been the identification of the methyl-CpG-binding domain family of proteins, which provide mechanistic links between specific patterns of DNA methylation and histone modifications. Interest in non-allelic histone variants has been renewed, in part because of recent work on H3 (and other) histone variants. However, only in mammals do three non-centromeric H3 variants (H3.1, H3.2, and H3.3) exist (1). Epigenetic changes underlie not only normal, but also pathological development. Bmi1 is recognized as a member of the PcG family of proteins (2). The PcG proteins function within distinct multisubunit complexes and epigenetically regulate gene expression by altering chromatin states at specific promoters. In concordance with its role in stem cells, Bmi-1 has been proposed to maintain cancer stem cell populations (3).
Pluripotent embryonic stem cells (ESCs) have the potential to produce every type of cell in the human body. Pluripotency is a unique epigenetic state, in that ESCs can self-renew, while retaining the potential for multilineage differentiation. OCT4 is highly expressed in pluripotent cells and becomes silenced upon differentiation. Interestingly, the precise expression level of OCT4 determines the fate of embryonic stem cells (4). Nevertheless, further investigations are required to fully elucidate the underlying molecular mechanisms responsible for the maintenance and initiation of pluripotency. Novus Biologicals offers an extensive collection of reagents to investigate epigenetic alterations, including Histone H3.2 K23me2 antibody (NB21-1162), Bmi1 antibody (NBP1-96140) and OCT4 antibody (NB100-2379) and our entire EpiPlus™ line.
- PMID: 16212490
- PMID: 1922340
- PMID: 12714970, PMID: 14574365
- PMID: 19480567
Tags: Bmi1, Bmi1 antibody, Chromatin Modifiers, DNA Methylation, Embryonic Stem Cell Marker, Embryonic Stem Cells, histone modification, Histone Modifications, Histones study, OCT4, Oct4 antibody, pluripotent, Pluripotent Embryonic Stem Cells
Posted in Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Cancer, Epigenetics, Stem Cells, Tumor | No Comments »
Friday, May 11th, 2012
Discovery of histone variants using highly specific antibodies has led to the emerging notion that alterations in histone modifications and further changes in chromatin structure are induced by exchange of histone variants. Covalent histone modifications and the incorporation of histone variants bring about changes in chromatin structure that in turn alter the gene expression. These modifications can be detected using highly specific antibodies, such as the Epi-Plus™ products from Novus.
Interest in non-allelic histone variants has been renewed, in part because of recent studies of H3 (and other) histone variants. However only in mammals do three non-centromeric histone H3 variants (H3.1, H3.2, and H3.3) exist. Studies have shown that the variants of histone H3 differ primarily in their chromatin deposition patterns and post- translational modifications (1). Additional studies using H3 antibodies have shown that the interplay among deposition of H3 variants likely participates in the functional organization of chromatin. Available literature suggests that dynamic replacement of histone variants plays an important role in genome remodeling during early development and that histone H3 proteins are highly conserved across all eukaryotes and are dynamically modified by post-translational modifications (2). Extreme conservation of known acetylation and methylation sites of lysines and arginines predicts that these post-translational modifications exist across the eukaryotes with canonical chromatin structures (3).
In a recent study using Histone H3 antibodies, methylated histone (H3) expressions in unexplained recurrent spontaneous abortion (URSA) and normal early pregnancy was found to be significantly lower (P < 0.0001) in URSA tissues than in controls as determined by immunohistochemistry and western blotting using Histone H3 antibodies (4), suggesting that methylation may cause URSA indicating the need for further work to explore the role of methylation in various disorders including cancer. Novus Biologicals offers a wide variety of study tools including antibodies, lysates, proteins and peptides for your research needs.
- PMID: 16212490
- PMID: 21998593
- PMID: 21910587
- PMID: 21606120
Tags: Chromatin Modifiers, EpiPlus, Histone H3, Histone H3 antibody
Posted in Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Epigenetics | No Comments »
Friday, December 16th, 2011
Histone modification is known to affect transcriptional access to chromatin. Therefore, high quality histone modification specific antibodies are necessary to understand and explain the specific roles that these epigenetic modifications play in transcription regulation. Unfortunately, many of the commercially available histone modification antibodies are designed against short immunizing peptides and lack specificity to the full-length modified histone.
In work presented at last week’s meeting of the Amercian Society for Cell Biology, researchers at 21st Century Biochemicals and Novus Biologicals developed a highly specific EpiPlusTM antibody line. These antibodies were then characterized in Western blot, ChIP and immunostain on full-length forms of various epigenetically modified Histone H3 and H4 to ensure specificity. ChIP testing was performed using Novus’ ChromataChIP kits. This thorough validation in various applications on full-length proteins ensures that the EpiPlusTM line is the best histone modification specific antibodies available on the market.
Source:
Fishman J, Homon A, Lamsa E, et al. The Complete Chemical Synthesis of Histones H3 and H4 Containing Epigenetic Modifications and Their Use in Characterizing Arginine Methylated Histone Antibodies. Poster presented at ASCB. 21st Century Biochemicals, Marlborough, MA 01752, Novus Biologicals, LLC, 8100 Southpark Way, Littleton, CO 80120
Tags: ChromataChIP, Epigenetics, EpiPlus, Histone
Posted in Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Epigenetics, Transcription Regulation | No Comments »
Thursday, December 15th, 2011
DNA methyltransferases catalyze the transfer of the methyl group from S-andenosyl methionine (SAM) to DNA. Such methylation has wide ranging function in the cell, including organismal development and cell differentiation. In cancer, abnormal hypermethylation of gene promoter CpG islands can result in transcriptional silencing. De novo methyltransferases methylate unmethylated DNA, this occurs primarily during early embryonic development and sets the methylation pattern for that cell. Maintenance methyltransferases methylate hemimethylated DNA and continues the methylation pattern set during development. In mammals there are three DNA methyltranferases, DNMT1, DNMT3a and DNMT3b. All 3 are involved in DNA methylation during development, as well as coordinating the methlylation of histone thus participating in epigenetic regulation. However, each protein plays a slightly different role in the cell.
DNMT1 (DNA (cytosine-5-)-methyltransferase 1) is the most abundant maintenance methyltrasferase and it preferentially methylates hemimethylated CpG residues. It also maintains DNA methylation independent of replication by associating with chromatin during the G2 and M phases. Recent research suggests that SIRT1 can alter DNMT1 activity by deacylation of lysine residues. Deacylation of different lysines alter DNMT1 activity in different ways. (PMID: 21947282)
DNMT3a (DNA (cytosine-5-)-methyltransferase 3 alpha) is a de novo methyltransferase. It is capable of methlyating non-CpG sites. It may also preferentially methylate the DNA linker positioned between 2 nucleosomal cores and be inhibited by histone H1. It also plays a role in the imprinting. Point mutations at the DNMT3a homotetramer interface causes the formation of homodimers. These mutants show a loss of processivity characteristic of patients with AML. (PMID: 21979949)
DNMT3b (DNA (cytosine-5-)-methyltransferase 3 beta) may be involved in the methylation of the DNA in the nucleosome core region. By associating with CBX4 it acts as a transcriptional co-repressor. Together DNMT1 and DNMT2b are involved in the activation of the BAG1 gene by modulating the dimethlyation of the promoter histone H3 at the H3K4 and H3K9 residues. (PMID: 18413740).
Novus is proud to offer top quality antibodies for all three of these methyltransferases for your research needs. DNMT1 (NB100-264), DNMT3 (NB100-265) and DNMT3b (NB100-266).
Tags: BAG1 antibody, DNA methyltransferase, DNMT1, DNMT1 antibody, DNMT3, DNMT3 antibody, DNMT3a, DNMT3a antibody, SIRT1, SIRT1 antibody
Posted in Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Epigenetics | No Comments »
Thursday, September 29th, 2011
Tubulin is a heterodimeric complex composed of alpha and beta subunits. Just like histones, tubulin can undergo post-translational modification, to affect cellular function. Novus Biologicals offers a large database of modified Tubulin antibody products.
Tubulin is the key building block of microtubules, found in practically all eukaryotic cells. The microtubules are essential to structure and mobility, being involved in mitosis, meiosis, flagella movement, organelle mobility, intracellular transport and cytoskeletal function. The detection, isolation and study of microtubular proteins, through alpha and beta Tubulin antibody research, are essential to the understanding of microtubule function.
Both the alpha and the beta tubulins have multiple isotypes, any of which can also undergo a number of post-translational modifications. These modifications, which are highly conserved in evolution, include acetylation, phosphorylation, detyrosination, polyglutamylation, and polyglycylation. Although these occur at less than 10% of tubulin residues, they have a marked effect on cellular activity, regulating specific microtubule functions either independently, or in combination.
These tubulin modifications are analogous to the role modified histones play in chromatin regulation. For example, Tubulin acetylation at lysine residue 40 is thought to play a role in cell motility, cell shape remodelling and the terminal branching of neurons. Just as modified histone antibodies play a vital role in epigenetics research, tubulin antibodies are similarly useful in the study of microtubule function. Therefore the Tubulin [ac Lys40] antibody, which detects endogenous Tubulin only when acetylated at the Lys40 residue, is a useful tool for research on any of these cellular processes.
Tags: microtubule, Tubulin
Posted in Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Epigenetics | No Comments »
Thursday, December 30th, 2010
MECP2 antibodies are used in DNA methylation studies as well as research into Rett syndrome, a progressive neurological disorder caused by a mutation in the MECP2 gene. Now, a new study has been published by the laboratory where the Rett Syndrome gene was discovered, citing MECP2 as a critical factor in a number of other neurological conditions by its interaction with GABA. We at Novus Biologicals have an extensive neuroscience antibody catalog which includes MECP2 antibodies.
MeCP2 is a complex member of the MBD family of proteins, related by the presence of a methyl- CpG domain and the ability to bind specifically to methylated DNA. It is found in large concentrations in neurons, where it functions as a transcriptional repressor, silencing transcription by binding to methylated promoters; however antibodystudies have suggested it may work as both a silencer and activator, through interaction with CREB1. A study by Georgel et al in 2003 also suggested MeCP2 may also bind to unmethylated DNA, while In 2007, Yasui, et al. published research suggesting that the primary function of MeCP2 is not, after all, to silence methylated promoters.
A number of different MECP2 mutations have been identified for Rett syndrome, causing suppressed DNA binding and abnormal expression of other proteins. However, MECP2 mutation has also been seen in X-linked retardation, neonatal encephalopathy, autism and other behavioural conditions. Now, a new study by Huda Zoghbi, using a novel mouse model, has shown that MeCP2 plays an essential role in modulating GABA expression in inhibitory neurons, thus linking it to other conditions like schizophrenia. Absence of the protein led to a wide range of neuropsychiatric symptoms, not limited to Rett syndrome. MeCP2 antibodies will play an important role in future GABA neuron studies.
Tags: DNA Methylation, GABA, GABA Antibody, MeCP2, MeCP2 antibody, Rett syndrome, Schizophrenia
Posted in Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Epigenetics, Neuroscience | No Comments »
Monday, November 29th, 2010
Forming the major protein component of chromatin, histones are essential to the structure and organization of chromosomes, forming the nucleosome around which DNA is packaged and wrapped.
Antibody studies have revealed histones undergo various posttranslational modifications which affect their interaction with DNA and nuclear proteins, allowing them to play diverse roles in biological processes such as cell division, gene regulation and DNA repair. For example, the outer “tail” of H3 and H4, and central core of H2A, H2B and H3 can undergo covalent modification via methylation, ubiquitination, phosphorylation and many other routes. These modifications constitute an epigenetic “histone code,” denoted by the name of the protein, the amino acid modified, and the type of modification. For example, H3K4me1 tells us that the histone H3 underwent monomethylation of lysine residue 4 (denoted by K4).
Research of histone modification in higher eukaryotes has been hampered by lack of a suitable experimental model. Now, researchers at Göttingen’s Max Planck Institute have succeeded in creating a genetic system that enables direct observation of histone modification and function in fruit flies, allowing both in vitro and in vivo effects to be studied. The system involves replacing the canonical histone complement of the flies with experimentally modified and coded histones from other organisms. This provides a direct cellular and antibody assay system, allowing in-depth analysis of histone modification on chromatin assembly, cell function, cell division and many other aspects of cell biology.
We at Novus Biologicals anticipate this new genetic tool will generate a lot of excitement among users of our antibody database.
Tags: Chromatin Modifiers, Chromatin Research, Drosophila Model, Histone Acetylation, Histone H3, Histone H4, Histone Methylation, Histone Modifications, Histone Phosphorylation, Histone Research, Histone Ubiquitination
Posted in Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Epigenetics | No Comments »
