 |
|
Conaway Lab Identifies Novel Mechanism for Regulation of Gene Expression
September 29, 2008The Stowers Institute's Conaway Lab has demonstrated that an enzyme called Uch37 is kept in check when it is part of a human chromatin remodeling complex, INO80. The results were published in today's issue of Molecular Cell.
Uch37 is a "deubiquitinating enzyme" that can remove protein tags (called ubiquitin) from other proteins. The presence of one kind of ubiquitin tag on a protein can mark it for destruction, but others serve as marks to affect the activity of a protein. INO80 is a chromatin remodeling complex that is believed to function in both gene regulation and DNA repair by "unpacking" DNA from nucleosomes to allow access to chromosomal DNA.
Previously, the Conaway Lab demonstrated that Uch37 is associated with another multiprotein complex, the proteasome - a large protein complex that degrades unneeded or damaged proteins. In the new paper, the team shows that when bound to INO80, Uch37 can also be activated in the presence of proteasomes. Although the mechanism involved isn't totally clear, it seems to occur via a "touch and go" mechanism, in which proteasomes interact transiently with Uch37.
"Our findings suggest that activation of INO80-associated Uch37 by transient association of proteasomes with the INO80 complex could be one way proteasomes help to regulate gene expression," said Tingting Yao, Ph.D., Postdoctoral Research Fellow and lead author on the paper.
"Tingting's discovery of communication between INO80 and the proteasome provides new clues into the functions of both of these regulatory complexes," said Joan Conaway, Ph.D., Investigator and senior author on the paper. "In addition, it provides new insights into how deubiquitinating enzymes can be regulated - the ability to regulate these enzymes is very important because promiscuous removal of ubiquitin marks could lead to a failure to regulate properly the activities or levels of key enzymes and proteins in cells."
The ultimate goal of the Conaway Lab is to understand how genes are turned on and off during transcription and how regulation of chromatin structure contributes to this process. Proper gene regulation is key for normal development and functioning of all organisms, including humans. Misregulation of gene expression can contribute to many diseases.
Additional contribution authors from the Stowers Institute include Jingji Jin, Ph.D., Senior Research Associate; Yong Cai, Ph.D., Research Specialist I; Hidehisa Takahashi, Ph.D., Postdoctoral Research Associate; Selene Swanson, Research Specialist II; Michael Washburn, Ph.D., Director of Proteomics; Laurence Florens, Ph.D., Managing Director of Proteomics; and Ron Conaway, Ph.D., Investigator. Contributing authors from other institutions include Ling Song, Ph.D., Carver College of Medicine, University of Iowa; and Robert Cohen, Ph.D., Bloomberg School of Public Health, Johns Hopkins University.
Drs. Joan and Ron Conaway hold faculty appointments in the Department of Biochemistry & Molecular Biology at The University of Kansas School of Medicine. Learn more about their work at www.stowers-institute.org/labs/ConawayLab.asp.
About the Stowers Institute
Housed in a 600,000 square-foot state-of-the-art facility on a 10-acre campus in the heart of Kansas City, Missouri, the Stowers Institute for Medical Research conducts basic research on fundamental processes of cellular life. Through its commitment to collaborative research and the use of cutting-edge technology, the Institute seeks more effective means of preventing and curing disease. The Institute was founded by Jim and Virginia Stowers, two cancer survivors who have created combined endowments of $2 billion in support of basic research of the highest quality.
Stowers Institute
"Our findings suggest that activation of INO80-associated Uch37 by transient association of proteasomes with the INO80 complex could be one way proteasomes help to regulate gene expression," said Tingting Yao, Ph.D., Postdoctoral Research Fellow and lead author on the paper.
"Tingting's discovery of communication between INO80 and the proteasome provides new clues into the functions of both of these regulatory complexes," said Joan Conaway, Ph.D., Investigator and senior author on the paper. "In addition, it provides new insights into how deubiquitinating enzymes can be regulated - the ability to regulate these enzymes is very important because promiscuous removal of ubiquitin marks could lead to a failure to regulate properly the activities or levels of key enzymes and proteins in cells."
The ultimate goal of the Conaway Lab is to understand how genes are turned on and off during transcription and how regulation of chromatin structure contributes to this process. Proper gene regulation is key for normal development and functioning of all organisms, including humans. Misregulation of gene expression can contribute to many diseases.
Additional contribution authors from the Stowers Institute include Jingji Jin, Ph.D., Senior Research Associate; Yong Cai, Ph.D., Research Specialist I; Hidehisa Takahashi, Ph.D., Postdoctoral Research Associate; Selene Swanson, Research Specialist II; Michael Washburn, Ph.D., Director of Proteomics; Laurence Florens, Ph.D., Managing Director of Proteomics; and Ron Conaway, Ph.D., Investigator. Contributing authors from other institutions include Ling Song, Ph.D., Carver College of Medicine, University of Iowa; and Robert Cohen, Ph.D., Bloomberg School of Public Health, Johns Hopkins University.
Drs. Joan and Ron Conaway hold faculty appointments in the Department of Biochemistry & Molecular Biology at The University of Kansas School of Medicine. Learn more about their work at www.stowers-institute.org/labs/ConawayLab.asp.
About the Stowers Institute
Housed in a 600,000 square-foot state-of-the-art facility on a 10-acre campus in the heart of Kansas City, Missouri, the Stowers Institute for Medical Research conducts basic research on fundamental processes of cellular life. Through its commitment to collaborative research and the use of cutting-edge technology, the Institute seeks more effective means of preventing and curing disease. The Institute was founded by Jim and Virginia Stowers, two cancer survivors who have created combined endowments of $2 billion in support of basic research of the highest quality.
Stowers Institute
Chromatin Remodeling Current Events and Chromatin Remodeling News RSSConaway Lab uncovers function of potential cancer-causing gene product
The Stowers Institute's Conaway Lab has uncovered a previously unknown function of a gene product called Amplified in Liver Cancer 1 (Alc1), which may play a role in the onset of cancer.
BRIT1 allows DNA repair teams access to damaged sites
Like a mechanic popping the hood of a car to get at a faulty engine, a tumor-suppressing protein allows cellular repair mechanisms to pounce on damaged DNA by overcoming a barrier to DNA access.
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.
Gladstone scientists identify key factors in heart cell creation
Scientists at the Gladstone Institute of Cardiovascular Disease have identified for the first time key genetic factors that drive the process of generating new heart cells.
Scripps Research Scientists Shed Light on How DNA Is Unwound So That Its Code Can Be Read
Researchers at The Scripps Research Institute have figured out how a macromolecular machine is able to unwind the long and twisted tangles of DNA within a cell's nucleus so that genetic information can be "read" and used to direct the synthesis of proteins, which have many specific functions in the body.
Once suspect protein found to promote DNA repair, prevent cancer
An abundant chromosomal protein that binds to damaged DNA prevents cancer development by enhancing DNA repair, researchers at The University of Texas M. D. Anderson Cancer Center report online this week in the Proceedings of the National Academies of Science.
Brain DNA 'remodeled' in alcoholism
Reshaping of the DNA scaffolding that supports and controls the expression of genes in the brain may play a major role in the alcohol withdrawal symptoms, particularly anxiety, that make it so difficult for alcoholics to stop using alcohol.
Gene-chip studies provide new leads in treating lung disease of premature newborns
Some 20 to 40 percent of extremely premature infants suffer abnormal lung development leading to bronchopulmonary dysplasia, a chronic lung disease that can cause long-term breathing problems.
Progress in understanding the malarial parasite
About 2 million people die of malaria every year, of which more than a million are children in sub-Saharan Africa. Malaria is caused by a protozoan parasite belonging to the genus Plasmodium, and Plasmodium falciparum is responsible for the most severe form of malaria.
Conaway Lab Demonstrates Mechanism by which Transcription Factor Controls Gene Expression
The Conaway Lab - led by Joan Conaway, Ph.D., and Ron Conaway, Ph.D., Investigators - has published findings that shed light on the role of the much-studied transcription factor YY1 in gene expression. Yong Cai, Ph.D., Research Specialist I, and Jingji Jin, Ph.D., Senior Research Associate, are the paper's coequal first authors.
More Chromatin Remodeling Current Events and Chromatin Remodeling News Articles
|
Genetics December 2001: Counteracting Regulation of Chromatin Remodeling Ata Fission Yeast Camp Responsive Element- Related Recombination Hotspot by Genetics (Author) | |
 |
Chromatin and Chromatin Remodeling Enzymes Part C, Volume 377 (Methods in Enzymology) by Carl Wu (Author), C. David Allis (Author) DNA in the nucleus of plant and animal cells is stored in the form of chromatin. Chromatin and the chromatin remodelling enzymes play an important role in gene transcription. *Genetic assays of chromatin modification and remodeling *Histone modifying enzymes *ATP-dependent chromatin remodeling enzymes |
 |
Chromatin and Chromatin Remodeling Enzymes, Part A, Volume 375: Methods in Enzymoglogy (Methods in Enzymology) by Carl Wu (Author), C. David Allis (Author) DNA in the nucleus of plant and animal cells is stored in the form of chromatin. Chromatin and the Chromatin remodellng enzymes play an important role in gene transcription. *Histone Bioinformatics *Biochemistry of histones, nucleosomes and chromatin *Molecular cytology of chromatin functions |
 |
Reversible Phosphorylation and Oocyte Maturation - Regulation of Germinal Vesicle Breakdown and Chromatin Remodeling by Jason Swain (Author) The delicate nature of reproduction is evidenced by the fact that the female gamete is notorious for having high rates of chromosomal abnormalities. It is estimated 10-25% of all human conceptions are chromosomally abnormal due to an error in chromosome segregation during meiosis. Furthermore, studies indicate greater than 95% of this human aneuploidy is attributable to defects within the meiotic machinery of the oocyte, rather than that of the sperm. This results in chromosomal non-disjunction leading to embryonic aneuploidy, miscarriage, infertility and congenital defects. Nevertheless, causative factors and intraoocyte biochemical signaling pathways causing these chromosomal perturbations are unknown. Therefore, elucidating regulatory mechanisms involved in oocyte meiosis is imperative... |
 |
Transposable Elements: A Guide to the Perplexed and the NoviceWith Appendices on RNAi, Chromatin Remodeling and Gene Tagging by E. Galun (Author) Studies during the first half of the 20th Century indicated that genes are entities that are located on fixed sites along the chromosomes. Then, due to the research of Barbara McClintock, mobile genetic elements were revealed in maize. While this discovery was initially regarded as a peculiarity, further studies revealed a completely different picture. It is now clear, that transposable elements (or elements that had the capability to be mobile in the past) exist in all organisms. These elements can change location and severely affect genes. In many organisms they even constitute the majority of the genetic material. There are two major classes of Transposable Elements: Class I elements that are mobilized with an RNA intermediate (retrotransposons), and Class II elements that... |
 |
Chromatin Dynamics in Cellular Function (Results and Problems in Cell Differentiation) by Brehon C. Laurent (Editor) This volume includes timely reviews of several aspects of chromatin biology written by scientists at the forefront of this rapidly moving field. Topics covered include the structure and function of protein modules within chromatin-remodeling proteins, newly characterized histone modifications (methylation, ubiquitylation) and their functional consequences, transcription and histone dynamics, roles of chromatin remodeling factors in DNA replication and repair, and current models of nucleosome-remodeling mechanisms. |
 |
Protein Complexes that Modify Chromatin. Current Topics in Microbiology and Immunology, No. 274 by Jerry L. Workman (Editor) This book provides timely reviews of several protein complexes that regulate gene expression and chromatin dynamics. Examples of such complexes include: nucleosome assembly complexes, ATP-dependent chromatin remodeling complexes, histone acetyltransferase complexes, histone deacetylase complexes, heterochromatin complexes, SMC complexes and transcription elongation complexes. These chapters will bring experts in the field up to date on several aspects of chromosome biology and will provide an exiting introduction to the field for new chromatin researchers. |
 |
Small RNAs:: Analysis and Regulatory Functions (Nucleic Acids and Molecular Biology) by Wolfgang Nellen (Editor), Christian Hammann (Editor) In recent years Molecular Biology has experienced an unprecedented revolution by the discovery of functional small RNAs. The number of cellular processes in which non-coding RNAs are involved is growing rapidly and include gene regulation on the transcriptional, post-transcriptional and translational level. To complicate matters, these processes seem to be strongly interconnected on the one hand, and diverse among different organisms on the other. This volume describes strategies for the discovery and validation of small RNAs and provides a snapshot of our current understanding of the different mechanisms triggered by small RNAs. |
|
Chromatin And Chromatin Remodeling Enzymes, Part A, Volume 375: Methods In Enzymoglogy (methods In Enzymology) by C. David Allis Carl Wu (Author) | |
|
Chromatin and Chromatin Remodeling Enzymes, Part B (Methods in Enzymology, Vol. 376) by C. David Allis Carl Wu (Author) |
| © 2009 BrightSurf.com |