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Shilatifard and colleagues identify a potential target for treatment of mixed lineage leukemia
March 12, 2007Ali Shilatifard, Ph.D., Investigator, has identified a cellular factor that can reverse histone trimethylation caused by the trithorax gene, the Drosophila homologue of the human mixed lineage leukemia gene, MLL. MLL, which is found in translocations in a variety of hematological malignancies, is a histone H3K4 methyltransferase.
The paper, "The trithorax-group gene little imaginal discs in Drosophila encodes a histone H3 trimethyl-Lys4 demethylase," was posted today in the Advanced Online Publication section of Nature Structural & Molecular Biology. The publication identified a cellular factor that can reverse histone trimethylation associated with mixed lineage leukemia. This, in turn, may allow for the identification of new targets for the treatment of leukemia caused by MLL translocations.
"This work demonstrates that a Drosophila gene product, little imaginal discs (Lid), removes methyl groups from histone H3K4," explains Dr. Shilatifard. "A reduction of Lid results in a specific genome-wide increase in H3K4 trimethylation levels with no effect on other patterns of histone trimethylations. Animals with reduced Lid levels have higher levels of H3K4 trimethylation, resulting in altered distribution of the chromo-helicase protein, the CHD1."
"Dr. Shilatifard's first publication since joining the Institute earlier this year is a fascinating one," said Robb Krumlauf, Ph.D., Scientific Director. "The role of MLL in a variety of blood-related cancers has been well-established. These findings give us a promising option for developing targeted treatments to combat these types of leukemia."
Stowers Institute for Medical Research
"Dr. Shilatifard's first publication since joining the Institute earlier this year is a fascinating one," said Robb Krumlauf, Ph.D., Scientific Director. "The role of MLL in a variety of blood-related cancers has been well-established. These findings give us a promising option for developing targeted treatments to combat these types of leukemia."
Stowers Institute for Medical Research
Histone Current Events and Histone News RSSNew research into the mechanisms of gene regulation
A team led by Penn State's Ross Hardison, T. Ming Chu Professor of Biochemistry and Molecular Biology, has taken a large step toward unraveling how regulatory proteins control the production of gene products during development and growth.
Is hepatic differentiation of embryonic stem cells induced by valproic acid and cytokines?
Embryonic stem (ES) cells, known for their capacity to proliferate indefinitely and differentiate into almost all types of cells including hepatocytes, have raised the hope of cellular replacement therapy for liver failure.
Researcher Solves Mystery about Proteins that Package the Genome
A Florida State University College of Medicine researcher has solved a century-old mystery about proteins that play a vital role in the transfer of the human genetic code from one cell to another. The discovery could lead to finding new ways to help the body fight a variety of diseases, including cancer.
Gerton Lab determines the composition of centromeric chromatin
The Stowers Institute's Gerton Lab has provided new evidence to clarify the structure of nucleosomes containing Cse4, a centromere-specific histone protein required for proper kinetochore function, which plays a critical role in the process of mitosis. The work, conducted in yeast cells, was published in the most recent issue of Molecular Cell.
Mechanism for potential Friedreich's ataxia drug uncovered
Using clever chemistry, a Scripps Research team has pinpointed the enzyme target of a drug group that stops the progression of the devastating disease Friedreich's ataxia in mice and may do the same for humans.
Raising the alarm when DNA goes bad
Our genome is constantly under attack from things like UV light and toxins, which can damage or even break DNA strands and ultimately lead to cancer and other diseases.
Universitat Autonoma de Barcelona researchers first to clone mice in Spain
Researchers at the Department of Cell Biology, Physiology and Immunology at Universitat Autònoma de Barcelona (UAB) are the first to have cloned mice in Spain. Cloe, Cleo and Clona are three female brown-coloured mice and were born respectively on 12 May, 3 June and 10 June.
'Shock and kill' research gives new hope for HIV-1 eradication
Latent HIV genes can be 'smoked out' of human cells. The so-called 'shock and kill' technique, described in a preclinical study in BioMed Central's open access journal Retrovirology, might represent a new milestone along the way to the discovery of a cure for HIV/AIDS.
MIT-led team IDs gene key to Alzheimer's-like reversal
A team led by researchers at MIT's Picower Institute for Learning and Memory has now pinpointed the exact gene responsible for a 2007 breakthrough in which mice with symptoms of Alzheimer's disease regained long-term memories and the ability to learn.
Shilatifard and colleagues clarify the enzymatic activity of factors involved in childhood leukemia
The Stowers Institute's Shilatifard Lab and colleagues have provided new insight into the molecular basis for H3K4 methylation, an activity associated with the MLL protein found in chromosomal translocation-based aggressive infant acute leukemias.
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Histone Deacetylases: Transcriptional Regulation and Other Cellular Functions (Cancer Drug Discovery and Development) by Eric Verdin (Editor) A panel of leading investigators summarizes and synthesizes the new discoveries in the rapidly evolving field of histone acetylation as a key regulatory mechanism for gene expression. The authors describe what has been learned about these proteins, including the identification of the enzymes, the elucidation of the enzymatic mechanisms of action, and the identification of their substrates and their partners. They also review the structures that have been solved for a number of enzymes-both alone and in complex with small molecule inhibitors-and the biological roles of the several histone deacetylases (HDAC) genes that have been knocked out in mice. |
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The Histone Code and Beyond: New Approaches to Cancer Therapy (Ernst Schering Foundation Symposium Proceedings) by S.L. Berger (Editor), O. Nakanishi (Editor), B. Haendler (Editor) Methylation of DNA at cytosine residues as well as post-translational modifications of histones, including phosphorylation, acetylation, methylation and ubiquitylation, contribute to the epigenetic information carried by chromatin. These changes play an important role in the regulation of gene expression by modulating the access of regulatory factors to the DNA. The use of a combination of biochemical, genetic and structural approaches has allowed demonstration of the role of chromatin structure in transcriptional control. The structure of nucleosomes has been elucidated and enzymes involved in DNA or histone modifications have been extensively characterized. Since deregulation of epigenetic marks has been reported in many cancers, a better understanding of the underlying molecular... |
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Histone acetylation, chromatin remodelling, transcription and nucleotide excision repair in S. cerevisiae: studies with two model genes [An article from: DNA Repair] by Y. Teng (Author), Y. Yu (Author), J.A. Ferreiro (Author), R. Waters (Author) This digital document is a journal article from DNA Repair, published by Elsevier in . The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser. Description: We describe the technology and two model systems in yeast designed to study nucleotide excision repair (NER) in relation to transcription and chromatin modifications. We employed the MFA2 and MET16 genes as models. How transcription-coupled (TCR) and global genome repair (GGR) operate at the transcriptionally active and/or repressed S. cerevisiae MFA2 locus, and how this relates to nucleosome positioning are considered. We discuss the role of the Gcn5p histone acetyltransferase, also associated with MFA2's transcriptional... |
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Histones: Webster's Facts and Phrases by Icon Group International (Author) Ever need a fact or quotation on "histones"? Designed for speechwriters, journalists, writers, researchers, students, professors, teachers, historians, academics, scrapbookers, trivia buffs and word lovers, this is the largest book ever created for this word. It represents a compilation of "single sentences" and/or "short paragraphs" from a variety of sources with a linguistic emphasis on anything relating to the term "histones," including non-conventional usage and alternative meanings which capture ambiguities. This is not an encyclopedic book, but rather a collage of statements made using the word "histones," or related words (e.g. inflections, synonyms or antonyms). This title is one of a series of books that considers all major vocabulary words. The entries in each book cover all... |
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The structure and biological function of histones (CRC uniscience series) by Lubomir S Hnilica (Author) | |
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Progress In Non Histone Protein Research by Bekhor (Author) | |
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Sirtuins (histone deacetylases III) in the cellular response to DNA damage-Facts and hypotheses [An article from: DNA Repair] by M. Kruszewski (Author), I. Szumiel (Author) This digital document is a journal article from DNA Repair, published by Elsevier in . The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser. Description: Histone deacetylases (HDAC) are an important member of a group of enzymes that modify chromatin conformation. Homologues of the yeast gene SIR2 in mammalian cells code type III histone deacetylases (HDAC III, sirtuins), dependent on NAD^+ and inhibited by nicotinamide. In yeast cells, Sir2 participates in repression of transcriptional activity and in DNA double strand break repair. It is assumed that certain sirtuins may play a similar role in mammalian cells, by modifying chromatin structure and thus, altering the... |
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DNA-PK is responsible for enhanced phosphorylation of histone H2AX under hypertonic conditions [An article from: DNA Repair] by T. Reitsema (Author), D. Klokov (Author), J.P. Banath (Author), P.L. Olive (Author) This digital document is a journal article from DNA Repair, published by Elsevier in . The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser. Description: Exposure of cells to hypertonic medium after X-irradiation results in a 3-4-fold increase in the phosphorylation of histone H2AX (@cH2AX) at sites of radiation-induced DNA double-strand breaks. This increase was previously associated with salt-induced radiosensitization and inhibition of repair of DNA double-strand breaks. To examine possible mechanisms for the increase in foci size, chemical inhibitors of kinase and phosphatase activity and cell lines deficient in ATM and DNA-PK, two kinases known to phosphorylate H2AX, were... |
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DNA-PK phosphorylates histone H2AX during apoptotic DNA fragmentation in mammalian cells [An article from: DNA Repair] by B. Mukherjee (Author), C. Kessinger (Author), J. Kobayashi (Author), B. Chen (Author) This digital document is a journal article from DNA Repair, published by Elsevier in 2006. The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser. Description: The phosphorylation of histone H2AX at serine 139 is one of the earliest responses of mammalian cells to ionizing radiation-induced DNA breaks. DNA breaks are also generated during the terminal stages of apoptosis when chromosomal DNA is cleaved into oligonucleosomal pieces. Apoptotic DNA fragmentation and the consequent chromatin condensation are important for efficient clearing of genomic DNA and nucleosomes and for protecting the organism from auto-immmunization and oncogenic transformation. In this study, we... |
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Histones and Other Nuclear Proteins by Harris Busch (Author) |
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