Navigation Links
UT MD Anderson scientists discover secret life of chromatin
Date:9/1/2011

HOUSTON -- Chromatin - the intertwined histone proteins and DNA that make up chromosomes constantly receives messages that pour in from a cells intricate signaling networks: Turn that gene on. Stifle that one.

But chromatin also talks back, scientists at The University of Texas MD Anderson Cancer Center report today in the journal Cell, issuing orders affecting a protein that has nothing to do with chromatin's central role in gene transcription - the first step in protein formation.

"Our findings indicate chromatin might have another life as a direct signaling molecule, that it can signal back to other proteins irrespective of gene transcription," senior author Sharon Dent, Ph.D., professor and chair of MD Anderson's Department of Molecular Carcinogenesis and director of the Center for Cancer Epigenetics.

In a series of yeast experiments, Dent and colleagues show that a signal through a histone protein regulates another protein called Dam1 that is involved in the separation of chromosomes during cell division.

Signaling cascades don't dead-end at DNA

"It's a basic change in our way of thinking about cell signaling that all signals go into the nucleus and dead-end at DNA, that they point to chromatin and stop," Dent said. "Our data show that's not the case. We have a new fundamental aspect of cellular regulation that we need to now explore." DNA is tightly intertwined with histones and assembled in histone/DNA units called nucleosomes along the connecting length of a string of DNA. This structure is often described as being like beads on a string.

Genes are turned on by transcription factors, proteins that attach to the gene's promoter region and order the gene to make an RNA copy of its DNA that can be translated into a protein. Histone proteins regulate access to genes, blocking or facilitating transcription.

Histones and other proteins are modified by the attachment of chemical groups to specific spots on the protein. Attachment of a methyl group (a carbon atom joined to three hydrogen atoms) to a histone can help or hinder gene transcription depending on where the methylation occurs on the histone, Dent said.

Crucial cross-talk between proteins

In a 2005 Cell paper, Dent and colleagues reported that a methyl group-transferring protein called Set1 methylates the protein Dam1, which is part of a structure that assists in the orderly separation of chromosomes during cell division.

Set1 is part of a protein complex that works along with multiple regulatory factors to facilitate transcription by attaching methyl groups to a specific histone, H3, which was the only previously known target of Set1.

Dent's team set out to discover the exact mechanism by which Set1 methylates Dam1. To their surprise, they found that Dam1 methylation does not depend on gene transcription, revealing news roles for proteins formerly thought to be involved only in that process.

Rather, the crucial step is the attachment of a single signaling molecule called ubiquitin to a histone protein called H2B. This event was known to direct addition of methyl groups to histone H3, but Dent's work indicates it is also required for methylation of Dam1.

Communication between H2B and Dam1 is the first such instance of cross-talk between histone and non-histone proteins, the authors report. The signaling connection between a chromatin change and a non-DNA-templated process such as chromosome separation is also new.

Connections between histone ubquitination and histone methylation also occur in human cells, and mutations in a protein highly related to Set1, called MLL, are involved in leukemia. Dent's work raises the possibility that histones can signal to non-histone proteins in human cells and that mismanagement of these events caused by MLL mutations might contribute to leukemia development.

Dent's group is looking for other proteins that might be affected by histone modifications in both yeast and human cells. And they are studying the details of Dam1 methylation and its function in chromosome separation.


'/>"/>
Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

Related medicine news :

1. David Anderson to discuss what model organisms can teach us about emotion
2. LodgeNet Healthcare Deploys Custom Education Solution for M. D. Anderson Cancer Center
3. M. D. Anderson develops tool to measure severity of chronic graft-vs.-host disease symptoms
4. Costly tests may not help detect bladder cancer recurrence, M. D. Anderson study finds
5. M. D. Anderson zeroes in on better way to predict prognosis in pediatric leukemia patients
6. M. D. Anderson receives 4.5 million grant, largest ever for study of yoga and cancer
7. NACDS' Anderson Says Retailers and Suppliers' “Health and Wellness Renaissance” is Creating a “Historic, Watershed Moment”
8. Anderson & Kriger Takes Donations to Families Affected by Baja's Easter Earthquake
9. Peg Fields to receive MD Andersons highest nurse-oncologist honor
10. MD Anderson keeps No. 1 cancer ranking in US News & World Report annual survey
11. UT MD Anderson study finds women treated for breast cancer while pregnant have improved survival
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... Cary, North Carolina (PRWEB) , ... June 26, 2016 , ... ... the release of a new product that was developed to enhance the health of ... harvested for centuries. , The two main herbs in the PawPaws Cat Kidney ...
(Date:6/25/2016)... ... June 25, 2016 , ... Austin residents seeking Mohs surgery services, can ... Surgery and to Dr. Russell Peckham for medical and surgical dermatology. , Dr. Dorsey ... cancer. The selective fellowship in Mohs Micrographic Surgery completed by Dr. Dorsey was under ...
(Date:6/25/2016)... ... , ... As a lifelong Southern Californian, Dr. Omkar Marathe earned his Bachelors ... Geffen School of Medicine at UCLA. He trained in Internal Medicine at Scripps Green ... hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had the opportunity to train ...
(Date:6/24/2016)... Los Angeles, CA (PRWEB) , ... June 24, 2016 , ... ... plastic surgery procedures that most people are unfamiliar with. The article goes on to ... known procedures, but also many of these less common operations such as calf and ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Pulmonary Hypertension Association ... it will receive two significant new grants to support its work to advance ... 25th anniversary by recognizing patients, medical professionals and scientists for their work in ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... June 23, 2016 Research and Markets ... Market - Forecast to 2022" report to their offering. ... method for the patients with kidney failure, it replaces the ... from the patient,s blood and thus the treatment helps to ... chloride in balance. Increasing number of ESRD ...
(Date:6/23/2016)... 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) ... Elecsys BRAHMS PCT (procalcitonin) assay as a dedicated testing ... With this clearance, Roche is the first IVD company ... for sepsis risk assessment and management. PCT ... PCT levels in blood can aid clinicians in assessing ...
(Date:6/23/2016)... , June 23, 2016 Bracket , ... launch its next generation clinical outcomes platform, Bracket eCOA (SM) ... held on June 26 – 30, 2016 in ... first electronic Clinical Outcome Assessment product of its kind to ... #715. Bracket eCOA 6.0 is a flexible platform ...
Breaking Medicine Technology: