Breaking News
November 18, 2018 - Unusual case of father-to-son HIV transmission reported
November 18, 2018 - FDA Approves Aemcolo (rifamycin) to Treat Travelers’ Diarrhea
November 18, 2018 - Poverty blamed on widening north-south gap in young adult deaths in England
November 18, 2018 - Progress in meningitis lags far behind other vaccine-preventable diseases, analysis shows
November 18, 2018 - Consensus Statement Issued on Management of Foot, Ankle Gout
November 18, 2018 - Fine particle air pollution is a public health emergency hiding in plain sight
November 18, 2018 - In-hospital mortality higher among patients with drug-resistant infections
November 17, 2018 - Research shines new, explanatory light on link between obesity and cancer
November 17, 2018 - FIND explores new diagnostic assays for confirmatory HCV diagnosis in community settings
November 17, 2018 - Tracking Preemies’ Head Size May Yield IQ Clues
November 17, 2018 - Scientists call for unified standards in 3-D genome and epigenetic data
November 17, 2018 - Lab Innovations 2018 has beaten all records by attracting 3,113 attendees
November 17, 2018 - Sexuality education before age 18 may reduce risk of sexual assault in college
November 17, 2018 - FDA approves antibacterial drug to treat travelers’ diarrhea
November 17, 2018 - Lab Innovations 2018 confirmed as a major hit with visitors, exhibitors and speakers
November 17, 2018 - Largest parasitic worm genetic study hatches novel treatment possibilities
November 17, 2018 - UCLA biologists uncover how head injuries can lead to serious brain disorders
November 17, 2018 - Static and dynamic physical activities offer varying protection against heart disease
November 17, 2018 - Obesity significantly increases risk of Type 2 diabetes and coronary artery disease
November 17, 2018 - People with rare cancers can benefit from genomic profiling, shows research
November 17, 2018 - NIH awards over $1.8 million to husband-and-wife doctors to test new breast cancer approach
November 17, 2018 - Four-in-one antibody used to fight flu shows promise in mice
November 17, 2018 - New approach allows pathogens to be starved by blocking important enzymes
November 17, 2018 - Higher body mass index could cause depression even without health problems
November 17, 2018 - Protein which plays role in sensing cell damage serves as new target to treat pulmonary hypertension
November 17, 2018 - FDA Approves Adcetris (brentuximab vedotin) in Combination with Chemotherapy for Adults with Previously Untreated Systemic Anaplastic Large Cell Lymphoma or Other CD30-Expressing Peripheral T-Cell Lymphomas
November 17, 2018 - ID specialist input improves outcomes for outpatient parenteral antimicrobial therapy
November 17, 2018 - UT Southwestern scientists selected to receive 2019 Edith and Peter O’Donnell Awards
November 17, 2018 - New clinical algorithm to help individuals manage type 2 diabetes when fasting during Ramadan
November 17, 2018 - Researchers identify LZTR1 as evolutionarily conserved component of RAS pathway
November 17, 2018 - Heart Disease Leading Cause of Death in Low-Income Counties
November 17, 2018 - Estrogen Levels Test: MedlinePlus Lab Test Information
November 17, 2018 - Research reveals link between immunity, diabetes
November 17, 2018 - Research shows how to achieve improved smoking cessation outcomes within California’s Medicaid population
November 17, 2018 - New study finds less understanding and implementation of patient engagement
November 17, 2018 - New shoe insole technology could help diabetic ulcers heal better while walking
November 17, 2018 - New method to extend cell division and immortalization of avian-derived cells
November 17, 2018 - Australian Academy of Science urges parents to vaccinate children against meningococcal disease
November 17, 2018 - Hot water treatment may help improve inflammation and metabolism in sedentary people
November 17, 2018 - Researchers produce 3D chemical maps of small biological samples
November 17, 2018 - Must Blood Pressure Rise Wth Age? Remote Tribes Hold Clues
November 17, 2018 - Noonan Syndrome
November 17, 2018 - Interventions to delay and prevent type 2 diabetes are underused, researchers say
November 17, 2018 - Hackathon prize winner seeks to remotely monitor patient skin conditions
November 17, 2018 - Research team identifies Ashkenazi Jewish founder mutation for Leigh syndrome
November 17, 2018 - Gene editing could be used to halt kidney disease in patients with Joubert syndrome
November 17, 2018 - Study uncovers link between gut disruption and aging
November 17, 2018 - Teens more likely to pick up smoking after exposure from friends and family
November 17, 2018 - Nicoya designate the Institute for Stem Cell Biology and Regenerative Medicine as the OpenSPR Centre of Excellence
November 17, 2018 - new horizon in dental, oral and craniofacial research
November 17, 2018 - How does poor air quality affect your health?
November 17, 2018 - New device can regulate children’s blood glucose more like natural pancreas
November 17, 2018 - Game-Changers in Western Blotting and Protein Analysis
November 17, 2018 - FDA announces new actions to limit sale of e-cigarettes to youth
November 17, 2018 - Warmer winter temperatures related to higher crime rates
November 17, 2018 - MCO places increasing emphasis on helping people find and access healthy food
November 17, 2018 - Group of students aim to improve malaria diagnosis using old smartphones
November 17, 2018 - Transplantation of feces may protect preterm children from deadly bowel disease
November 17, 2018 - Researchers explore whether low-gluten diets can be recommended for people without allergies
November 17, 2018 - New and better marker for assessing patients after cardiac arrest
November 17, 2018 - For 7-year-old with failing bone marrow, a life-saving transplant | News Center
November 17, 2018 - New first-line treatment for peripheral T-cell lymphoma approved by FDA
November 17, 2018 - Artificial intelligence could be valuable tool to help young victims disclose traumatic testimony
November 17, 2018 - Breakthrough in the treatment of Restless Legs Syndrome
November 16, 2018 - FDA Approves Keytruda (pembrolizumab) for the Treatment of Patients with Hepatocellular Carcinoma (HCC) Who Have Been Previously Treated with Sorafenib
November 16, 2018 - Eagle Books | Native Diabetes Wellness Program
November 16, 2018 - Patients with common heart failure more likely to have lethal heart rhythms
November 16, 2018 - How AI could help veterinarians code their notes | News Center
November 16, 2018 - Bias-based bullying does more harm to students than generalized bullying
November 16, 2018 - Researchers find first direct evidence that cerebellum plays role in cognitive functions
November 16, 2018 - Non-coding genetic variant plays key role in endothelial function and disease incidence
November 16, 2018 - EMA recommends first all-oral treatment to tackle deadly sleeping sickness
November 16, 2018 - Drug used to treat dizziness may slow down growth of triple-negative breast cancer
November 16, 2018 - AHA: Icosapent Ethyl Cuts CV Risk From Elevated Triglycerides
November 16, 2018 - ‘Orphan’ RNAs make cancer deadlier, but potentially easier to diagnose
November 16, 2018 - Air Cube touches down at hospital | News Center
November 16, 2018 - CRISPR-based tool shown to enhance cell-based immunotherapy
November 16, 2018 - Mechanisms that govern HIV latency differ in the gut and blood, finds study
November 16, 2018 - Researchers unravel mystery of NPM1 protein in acute myeloid leukemia
November 16, 2018 - High school students less likely to select milk, fruit for lunch when fruit juice is available
Three-dimensional organization of genome plays key role in gene expression, cell fate

Three-dimensional organization of genome plays key role in gene expression, cell fate

image_pdfDownload PDFimage_print

Scientists have long been reading the code of life – the genome -, as a sequence of letters but now researchers have also started exploring its three-dimensional organization. In a paper published in Nature Genetics, an interdisciplinary research team of scientists from the Centre for Genomic Regulation (CRG) – including a Centro Nacional de Análisis Genómico (CNAG-CRG) group – in Barcelona, Spain, shows that the three-dimensional organization of the genome plays a key role in gene expression and consequently in determining cell fate.

It all began with the 4D Genome project, an ambitious and innovative research initiative funded by a European Research Council Synergy grant aimed at understanding how the spatial organization of the genome contributes to decisions made by cells. What scientists wanted to find out was whether genome architecture plays an active function or whether it is a mere side effect of the genome’s activity. The model that the 4D Genome team used was cell reprogramming, a process that allows the scientists to revert white blood cells back to a state of pluripotency whereby these cells can differentiate into any other cell type. Proteins that control gene activity (known as transcription factors) play a key role in this process, which the 4D Genome team studied in great detail, assessing how they induce changes in gene expression, modifications of chromatin (the structure around which DNA is wrapped), and changes in the 3D organization of the genome.

Understanding how stem cells are formed and how they can convert into different cell types is a major challenge in modern biology. It has been known since the fifties that all specialized cells in the body contain the same genome. So, what then distinguishes one cell type from another? The answer is that different cells read the information contained in different parts of the genome. The machinery required to achieve this selective information recall resides primarily in so called ‘transcription factors’, molecules that switch genes on or off. Many other molecules are also involved in this process, including epigenetic regulators that help to densely pack the genome into the nucleus of a cell, or locally unpack it to allow gene expression. The scientists used a reprogramming method discovered by CRG senior researcher Thomas Graf and his team. With this precision tool in hand, they were able to study the dynamics of genome organization by comparing the changes in genome architecture and transcription at different times during reprogramming.

“We expected that transcription factors would first switch on certain genes, which then afterwards may force a re-organization of the 3D structure of the chromosome. Surprisingly, what we found is that in a large proportion of the genome, the transcription factors were actually promoting this re-organization before the genes were switched on,” explains Ralph Stadhouders, co-first author of the paper together with computational biologist Enrique Vidal.

“Our paper shows that transcription factors may play a completely new role in cell reprogramming: they do not only switch genes on and off, but also promote the architectural changes necessary to modify gene expression,” states Thomas Graf, senior CRG group leader and lead investigator of this study. “It may have relevant implications for researchers worldwide studying gene regulation in general since we know now that the large-scale organization of the genome cannot be ignored. It also raises new questions about how these large changes can be brought about: possibly new mechanisms, perhaps even new machineries that are necessary to change certain areas of the genome” reflects Graf.

The perfect combination: risky + interdisciplinary fundamental science

The findings reported in Nature Genetics indicate that genome architecture has important informational value for controlling gene expression during cell reprogramming, and is thus required for the specialized functions of a cell. “We are only scratching the surface of what could be critical as yet unrecognized mechanisms by which cells regulate gene expression” says co-principal investigator and ICREA research professor at CNAG-CRG, Marc A. Martí-Renom. “The new discovery might also be fundamental for development and for some development-related diseases and cancer,” he concludes.

Again, this is an example on how risky science with innovative and interdisciplinary approaches leads to surprising and relevant results to advance knowledge. In this case, four laboratories at the Centre for Genomic Regulation (including a CNAG-CRG one) took full advantage of their experience and diverse capabilities to address fundamental questions in genome biology with the support of a 13M € ERC Synergy grant. “Promoting and supporting fundamental research is crucial to advance knowledge. We are proud that our project is already providing the first answers to the burning question about how genome 3D organization shapes genome regulation,” agree the four group leaders participating in the 4D Genome project: Thomas Graf, Marc A. Martí-Renom, Guillaume Filion, and Miguel Beato.

Tagged with:

About author

Related Articles