Navigation Links
Manipulating chromatin loops to regulate genes may offer future treatments for blood diseases
Date:6/7/2012

In exploring how proteins interact with crucial DNA sequences to regulate gene activity, researchers have shed light on key biological events that may eventually be manipulated to provide new disease treatments.

Within a cell's nucleus, regulatory elements in DNA called promoters and enhancers communicate with each other in carrying out gene activity, often over large genomic distances, hundreds of thousands of chemical bases apart from each other in chromosomes. As these elements physically contact each other, the intervening DNA sequences bend into loops made of chromatin fiberthe substance of chromosomes.

"Many researchers, including ourselves, have shown that chromatin looping is widespread during gene expression," said study leader Gerd A. Blobel, M.D., Ph.D., holder of the Frank E. Weise III Endowed Chair in Pediatric Hematology at The Children's Hospital of Philadelphia. "However, many details remain uncertaineven whether chromatin loops are a cause or effect of gene transcription. Our current study investigated some of these fundamental questions."

Blobel and first author Wulan Deng, a Ph.D. student at the University of Pennsylvania, are publishing their study in the June 8, 2012 print edition of Cell.

The study focused on gene transcriptionthe fundamental process by which information encoded in a gene's DNA is converted into RNA before the RNA information is translated into a protein.

Blobel and Deng used blood-forming cells in mice, studying a portion of DNA called the beta-globin locus that expresses part of the hemoglobin molecule. The study team already knew that a chromatin loop forms when a distant enhancer touches the promoter in the beta-globin gene and gives rise to gene expression. They did not know all the proteins that were necessary to generate chromatin loops, nor exactly how such proteins functionally interact with other proteins during gene transcription.

The study team sought to identify a looping factor, a protein that triggers chromatin looping. "We had a strong candidate for a looping factora molecule called Ldb1," said Deng. In the current study, Blobel and Deng made use of a specialized tool--a genetically engineered DNA binding protein called a zinc finger (ZF) protein, designed to specifically latch onto a chosen gene location.

They attached Lbd1 to a ZF, thereby tethering it to the target site in the beta-globin promoter. This caused a chromatin loop to form between the enhancer and promoter and allowed high-level gene transcription to occur.

"We showed that Ldb1 is a key factor in these long-range chromatin interactions that drive gene expression," said Blobel. "Moreover, our results suggest that chromatin looping is a cause, not an effect, of gene transcription. We will further study whether and how we can use forced chromatin looping to manipulate gene expression for scientific or therapeutic purposes."

Potential therapeutic implications: "One possible application of forced chromatin looping," added Blobel, "might be in hemoglobin diseases. For example, hematologists have a long-standing goal of reactivating dormant fetal hemoglobin genes to benefit children and adults with sickle cell anemia. It is worth testing whether our approach might force cells to produce fetal hemoglobin and treat sickle cell disease." More broadly, he added, forced chromatin looping might also enable researchers to turn off the expression of specific genes known to drive particular diseases.


'/>"/>
Contact: John Ascenzi
ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert  

Related biology news :

1. Crystal structure of archael chromatin clarified in new study
2. Law that regulates shark fishery is too liberal: UBC study
3. Gut microbiota regulates bile acid metabolism
4. Planarian genes that control stem cell biology identified
5. Culprit behind unchecked angiogenesis identified
6. Researchers identify genes that may help in ovarian cancer diagnosis and prognosis
7. Study finds peoples niceness may reside in their genes
8. Direct transfer of plant genes from chloroplasts into the cell nucleus
9. Large international study finds memory in adults impacted by versions of 4 genes
10. BUSM researchers identify genes that influence hippocampal volume
11. International team uncovers new genes that shape brain size, intelligence
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Manipulating chromatin loops to regulate genes may offer future treatments for blood diseases
(Date:5/16/2017)...  Veratad Technologies, LLC ( www.veratad.com ), an innovative ... verification solutions, announced today they will participate as a ... thru May 17, 2017, in Washington D.C.,s ... Identity impacts the lives of billions ... evolving digital world, defining identity is critical to nearly ...
(Date:4/18/2017)... Calif. , April 18, 2017  Socionext Inc., a global ... of a media edge server, the M820, which features the company,s ... recognition software provided by Tera Probe, Inc., will be showcased during ... at the NAB show at the Las Vegas ... ...
(Date:4/11/2017)... DUBLIN , Apr. 11, 2017 Research ... Tracking Market 2017-2021" report to their offering. ... The global eye tracking market to grow at ... The report, Global Eye Tracking Market 2017-2021, has been prepared based ... report covers the market landscape and its growth prospects over the ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... a leading provider of patient support solutions, has announced the ... which will launch this week. The VMS CNEs will address ... enhance the patient care experience by delivering peer-to-peer education programs ... to help women who have been diagnosed and are being ... ...
(Date:10/11/2017)... (PRWEB) , ... October 11, 2017 , ... ... compared the implantation and pregnancy rates in frozen and fresh in vitro ... of progesterone and maternal age to IVF success. , After comparing the results ...
(Date:10/10/2017)... (PRWEB) , ... October 10, ... ... development-stage cancer-focused pharmaceutical company advancing targeted antibody-drug conjugate (ADC) therapeutics, today confirmed ... targeted HPLN (Hybrid Polymerized Liposomal Nanoparticle), a technology developed in collaboration with ...
(Date:10/10/2017)... Oct. 10, 2017 International research firm Parks Associates ... speak at the TMA 2017 Annual Meeting , October 11 in ... the residential home security market and how smart safety and security products ... Parks Associates: Smart ... "The residential security market ...
Breaking Biology Technology: