Breaking News
October 22, 2018 - The International Society of Refractive Surgery honors Vivior Chairman with Casebeer Award
October 22, 2018 - Multi-strain probiotic helps reduce chemotherapy-induced diarrhea in cancer patients
October 22, 2018 - Study shows potential of avelumab plus axitinib as new treatment option for patients with advanced RCC
October 22, 2018 - Vertex gets European CHMP positive opinion for KALYDECO to treat patients with cystic fibrosis
October 22, 2018 - Phase III trial reports positive results with HDAC inhibitor in advanced breast cancer patients
October 22, 2018 - Prostate radiotherapy improves survival in men with low burden of metastatic disease
October 22, 2018 - Free phone app helps low-income obese patients to lose weight
October 22, 2018 - Compression Collar May Protect Brain of Female Soccer Players
October 22, 2018 - Technique visualizes neuron communication
October 22, 2018 - Advancement in medical imaging methods for health care
October 22, 2018 - Takeda presents vedolizumab phase 3 VISIBLE 1 trial results for treatment of moderately to severely active ulcerative colitis
October 22, 2018 - Immunotherapy increases survival in some patients with metastatic triple negative breast cancer
October 22, 2018 - Exelixis presents CABOSUN and METEOR trial results in patients with advanced renal cell carcinoma
October 22, 2018 - LYNPARZA Phase III SOLO-1 results show improved outcome for patients with advanced BRCA-mutated ovarian cancer
October 22, 2018 - Brainlab unveils ExacTrac Dynamic at ASTRO meeting in San Antonio, Texas
October 22, 2018 - Not exercising is worse than smoking, diabetes or heart disease finds study
October 22, 2018 - Shorter course of trastuzumab could be an option for women with HER2+ early breast cancer
October 22, 2018 - Map of Mouse Hippocampus Could Be Weapon Against Alzheimer’s
October 22, 2018 - Psychotropic polypharmacy is common in Alzheimer’s disease
October 22, 2018 - Texas A&M and UTA establish Texas Genomics Core Alliance
October 22, 2018 - Analyzing mouse’s potential as animal model of decision-making
October 22, 2018 - Radiotherapy can prolong survival in prostate cancer
October 22, 2018 - A genetic mutation involved in relapse
October 21, 2018 - Report reveals growing impact of cannabis on young people
October 21, 2018 - NSF awards $5 million grant to help scientists magnify societal impact of research
October 21, 2018 - Fertility Rates Down for Each Urbanization Level 2007 to 2017
October 21, 2018 - Genetically engineered 3-D human muscle transplant in a murine model
October 21, 2018 - Moms’ tight work schedules may affect their children’s sleep
October 21, 2018 - AHA: No Direct Link Between Preeclampsia and Cognitive Impairment, Study Finds
October 21, 2018 - Weight loss success linked with active self-control regions of the brain
October 21, 2018 - Scripps researchers successfully test potential new smoking-cessation treatment in rodents
October 21, 2018 - More accurate and less stressful way to measure a baby’s heartbeat
October 21, 2018 - Researchers show better cardiorespiratory fitness leads to longer life
October 21, 2018 - Healthy candies for diabetic patients
October 21, 2018 - Environment impact of microplastics remains unclear
October 21, 2018 - Antibiotics for appendicitis? Surgery often not needed
October 21, 2018 - AHA and AMA recognize more than 800 medical practices, health systems for blood pressure control
October 21, 2018 - Scientists obtain clearest ever image of Ebola virus protein
October 21, 2018 - Study reveals connection between two proteins known to be hyperactive in cancer
October 21, 2018 - Gabapentin Beats Pregabalin for Chronic Sciatica
October 21, 2018 - Cosmetic surgeons offering incomplete information for breast augmentation customers
October 21, 2018 - Chronic sleep disruption in early adult life accelerates AD-related tau pathology
October 21, 2018 - Take 10 for Mindfulness – Drugs.com MedNews
October 21, 2018 - Length of breathing disruption in OSA may be better predictor of mortality risk
October 21, 2018 - ApoE4 gene linked with chronic inflammation increases risk for Alzheimer’s disease
October 21, 2018 - Mother-daughter conflict associated with suicide risk in abused adolescent girls
October 21, 2018 - Scientists molding bacteria into unnatural shapes
October 21, 2018 - High diet quality associated with lower risk of death in colorectal cancer patients
October 21, 2018 - Discharged mental health patients ‘at greater risk of dying’
October 21, 2018 - Research provides insight into neurobiology of aggression and bullying
October 21, 2018 - As billions in tax dollars flow to private Medicaid plans, Who’s minding the store?
October 21, 2018 - Neuroscientists identify brain region that appears to be related to food preference decisions
October 21, 2018 - Deaths related to air pollution in the U.S. decreased by 47% between 1990 and 2010
October 21, 2018 - Study shows correlation between spatial memory and the sense of smell
October 21, 2018 - Increased cardiorespiratory fitness associated with reduced long-term mortality
October 21, 2018 - IU researchers receive $1.55 million from NIH to improve chronic-disease management
October 21, 2018 - Income and wealth affect the mental health of Australians, study shows
October 21, 2018 - Patients with hypertension and psoriasis more often require cardiovascular interventions
October 20, 2018 - Leading hip-hop videos depict use of tobacco and marijuana products, study finds
October 20, 2018 - Dose Range of IV Ketamine for Adjunct Tx of Depression Tested
October 20, 2018 - Infants can distinguish between leaders and bullies, study finds
October 20, 2018 - Mad Cow disease found on Aberdeenshire farm
October 20, 2018 - Study identifies factors associated with prescription opioid misuse among students
October 20, 2018 - Scientists uncover key regulator of mTORC1 in cancer growth
October 20, 2018 - Pounds Regained After Weight-Loss Op Can Tell Your Doc a Lot
October 20, 2018 - Sending parents letters to fight childhood obesity doesn’t work
October 20, 2018 - Supervised aerobic exercise can support major depression treatment
October 20, 2018 - Mindfulness-based program effective for reducing stress in infertile women
October 20, 2018 - Molecule capable of halting and reverting neurodegeneration caused by Parkinson’s disease identified
October 20, 2018 - Midazolam-mediated alterations of PER2 expression may have functional consequences during myocardial ischemia
October 20, 2018 - Sweat bees are ideal for studying the genes underlying social behavior
October 20, 2018 - Weight loss success associated with brain areas involved in self-control
October 20, 2018 - KHN’s ‘What the Health?’ Republicans’ preexisting political problem
October 20, 2018 - Research provides a more complete picture of suffering caused by terrorist attacks
October 20, 2018 - Eradicating Helicobacter pylori infections may be a key treatment for Parkinson’s disease
October 20, 2018 - Breast Cancer as a Dynamic Disease
October 20, 2018 - University of Pittsburgh wins NSF grant for big data research to prevent complications from anesthesia
October 20, 2018 - Skin-to-skin contact may promote attachment between parents and preterm infants
October 20, 2018 - Recommendations Developed to Verify NGT Placement in Children
October 20, 2018 - Weight loss can be boosted fivefold thanks to novel mental imagery technique

‘Icebreaker’ protein opens genome for T cell development, researchers find

image_pdfDownload PDFimage_print
TCF-1 is like an icebreaker ship that initially opens the ice (condensed, closed chromatin) and keeps a path available for other ships (other transcription factors that work in later stages of development) to steam through the now-open water (unwound chromatin). Credit: Stacie Leigh Bumgarner

Almost all cells in the human body have identical DNA sequences, yet there are 200-plus cell types with different sizes, shapes, and chemical compositions. Determining what parts of the genome are read to make protein and which are silenced is orchestrated by proteins called transcription factors. These regulate the availability of distinct stretches of DNA to be expressed as opposed to others that remain buried in tightly coiled structures called chromatin.

Researchers in the Perelman School of Medicine at the University of Pennsylvania, describe this week in Immunity the role of a transcription factor called TCF-1 in targeting the condensed chromatin and regulating the availability of genome sequences in T-cell development. The new connection between TCF-1 and chromatin will aid in developing new therapies using epigenetic drugs to alter T-cell fate in cancer, autoimmune disorders, and infectious diseases.

Senior author Golnaz Vahedi, PhD, an assistant professor of Genetics, brings her multidisciplinary training in computational biology, epigenetics, and immunology to bear on the question of T-cell identity. She leads a multidisciplinary team integrating computational and experimental approaches to develop an understanding of gene regulation in immune cells. Vahedi is also a member of Penn’s Institute for Immunology and Epigenetics Institute.

She likens TCF-1 to an icebreaker ship that initially opens the ice (condensed, closed chromatin) and keeps a path available for other ships (other transcription factors that work in later stages of development) to steam through the now-open water (unwound chromatin). TCF-1 ultimately opens chromatin so that DNA can be read to make proteins, and it also keeps chromatin open so that subsequent factors can access DNA to make protein that guide a maturing T cell to its final identity.

TCF-1 opens chromatin so that DNA can be read to make proteins, and keeps chromatin open so that subsequent factors can access DNA to make protein that guide a maturing T cell to its final identity. Credit: The lab of Golnaz Vahedi, PhD, Perelman School of Medicine at the University of Pennsylvania

Although the functional importance of TCF-1 in T cells has been known for more than 25 years, the mechanism by which this protein controls T-cell identity remained unknown. The team generated a profile of open and closed areas in eight stages of T-cell development and found an abundance of the transcription factor TCF-1 at regions along the genome that were open at the earliest stages of development.

“Our lab is interested in understanding how T-cell identity is established,” Vahedi said. “We chose to study T cells because of their all-important role in patrolling the body to clear it of germs and such other dangers as cancer cells.”

They established the identity-making role for TCF-1 by deleting it in a mouse model and found that most open sites closed, becoming inaccessible in tightly wound chromatin. On the other hand, when they added TCF-1 to a type of common skin cell, it “broke the ice” and opened closed regions by removing chemical groups that tighten chromatin. The elongated fibroblasts reprogrammed to become more T-cell-like in shape and hundreds of T-cell genes were also expressed in these skin cells.

Using computational and epigenomic methods, the team found that TCF-1 behaved in a similar manner on the chromatin of individual T cells. Because of the consistency among many cells, they concluded that TCF-1 control of T-cell fate is fundamentally important in determining what a cell will become.

“We showed how TCF-1 controls T-cell fate through its ability to target closed chromatin and establish the identity of developing T cells,” Vahedi said. “TCF-1 is the focus of many immunology and oncology studies, especially those dealing with checkpoint inhibitors and sick immune cells. We think that the ‘ice-breaking’ ability of TCF-1 can be selectively harnessed to reset ‘old’ T cells to a ‘younger’ state so they can fight invaders again.”


Explore further:
Recycling histones through transcription

Journal reference:
Immunity

Provided by:
Perelman School of Medicine at the University of Pennsylvania

About author