Navigation Links
Without this protein, embryonic development halts
Date:5/13/2010

Chromosome 22q11 deletion syndrome (also known as DiGeorge syndrome) is the most common human chromosome deletion syndrome, having an estimated incidence of at least one in 4,000 live births. It has a range of severity but a multisystem impact, with symptoms that may include congenital heart defects, immunologic and endocrine abnormalities, cleft palate, gastrointestinal problems, and neuropsychiatric abnormalities.

Nearly three-quarters of patients identified with this deletion syndrome have cardiac defects, and research into the underlying biology of this disorder has uncovered new knowledge of biological processes in both congenital heart disease and early embryonic development.

In the May 2010 issue of Experimental Biology and Medicine, Jason Z. Stoller, M.D., of The Children's Hospital of Philadelphia, collaborating with Jonathan A. Epstein, M.D., scientific director of the Penn Cardiovascular Institute of the University of Pennsylvania, report on an important interaction of two proteins, Ash2l and Tbx1, during early mammalian development. "In humans and other mammals, the heart is among the first organs to develop," said Stoller. "Greater knowledge of biological events that occur in the earliest stages of development helps us to better understand both normal and abnormal heart development."

In cell and animal studies, the researchers discovered that Ash2l, a core component of a protein complex responsible for epigenetic modifications, is absolutely essential to early embryogenesis; without this protein, mouse embryos did not survive past the first few days of gestation.

The region of chromosome 22 that is most commonly lost in DiGeorge syndrome contains more than 30 genes, among them the gene for the transcription factor Tbx1. The Tbx family of nuclear transcription factor proteins shares a T-box, a conserved DNA binding domain that mediates regulation of downstream genes. In 2005, Epstein and Stoller identified a domain within the Tbx1 protein that, when not functioning properly, plays a key role in causing DiGeorge syndrome in a subset of patients.

The current study aimed to identify proteins that interact with Tbx1 in a functionally important way that could shed light on the pathogenesis of DiGeorge syndrome. Using a yeast and cell culture studies, the researchers pinpointed the Ash2l protein as interacting with Tbx1. They then generated Ash2l knockout mice to further investigate the role of the Ash2l protein. Mouse embryos that did not express Ash21 died early in gestationdemonstrating that the protein is necessary for early development.

"The crucial requirement of the Ash2l protein", said Stoller, "suggests that it likely acts to regulate many developmental genes in mammals. As part of a histone methyltransferase complex, it regulates gene transcription by epigenetic mechanisms".

Future clinical implications for children and adults with DiGeorge syndrome are yet unclear. These patients have a normal Ash2l gene, but the loss of Tbx1 may alter the interaction between Ash2l and Tbx1 and play a role in their disease, possibly by regulating downstream genes. Stoller added, "The fact that patients with this genetic syndrome are missing a copy of the Tbx1 gene suggests that reduced amounts of the Tbx1 protein may have biological effects that cause different features of the disease. Further research is needed to discover these specific mechanisms."

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said "Stoller et al have demonstrated that protein Ash2l is essential in early embryogenesis. Ash2l interacts with the transcription factor Tbx1 which resides in a chromosomal region commonly deleted in DiGeorge syndrome. This interesting study suggests possible mechanisms leading to congenital heart disease in DiGeorge syndrome."


'/>"/>

Contact: John Ascenzi
ascenzi@email.chop.edu
267-426-6055
Society for Experimental Biology and Medicine
Source:Eurekalert

Related medicine news :

1. Enjoy Pregnancy Without Foot Pain: Foot and Ankle Surgeon Offers Guidelines
2. Myth Debunked: Baby Shower Gifts CAN Be Personalized Without Knowing Name Or Gender
3. Love handles repurposed for breast reconstruction in women without enough belly fat
4. Epione Helps Women Get Ready for Bikini Season without Hitting the Gym
5. Recent Studies Show MAstertuck℠ Technique Removes Large Amounts of Body Fat without Tummy Tuck Surgery
6. Real Men Don't Take Erectile Dysfunction Drugs Without a Prescription
7. SensiblyCelibate.com Encourages Relationships Without the Pressures of Becoming Intimate Too Prematurely
8. Should Cholesterol Drugs Be Used By Those Without High Cholesterol?
9. Pregnant women can receive breast cancer chemotherapy without endangering health of their babies
10. Adritech Software Releases Website Realizer, a Website Builder to Create Websites without Any Programming Knowledge
11. Palladians Distinguished Clinicians Present at APTAs National CSM Convention in San Diego on Evidenced Informed Management of Chronic Low Back Pain Without Surgery
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/11/2016)... ... February 11, 2016 , ... Greenfield ... charity program created to assist the people of their local community. The agency ... organizations and community leaders. Their hope is to bring awareness to important local ...
(Date:2/11/2016)... ... February 11, 2016 , ... ... Village Family Practice , will be presenting at the 2016 HIMSS Annual Conference ... Nev. , During his session, “ Coding for Care: Using Data Analytics ...
(Date:2/11/2016)... ... February 11, 2016 , ... The annual list showcases the ... of DataPoint’s team dedication and commitment to the SharePoint ecosystem. A panel ... list. The panel’s goal is to recognize and promote technology entrepreneurship. , The ...
(Date:2/11/2016)... Washington, D.C. (PRWEB) , ... February 11, 2016 ... ... will be exhibiting at the American Academy of Dermatology Annual Meeting at ... Hidrex USA's goal is to raise awareness for both the condition of hyperhidrosis ...
(Date:2/11/2016)... , ... February 11, 2016 , ... ... become more actively engaged in health and wellness best practices in the past ... riding this trend. February is American Heart Month, which acts as an exceptional ...
Breaking Medicine News(10 mins):
(Date:2/11/2016)...  MiMedx Group, Inc. (NASDAQ: MDXG ), the ... other birth tissues, human skin and bone, and patent-protected ... products and therapies, announced today that it will present ... in New York , NY.  Parker ... Senken , Chief Financial Officer and Chris Cashman ...
(Date:2/11/2016)... Feb. 11, 2016 Wearable posture tracker, ALEX , has taken Kickstarter by storm, crowdfunding ... seven days left to go, ALEX is said to be delivered to backers starting May of this ... ... ... Created by NAMU, a ...
(Date:2/11/2016)... INDIANAPOLIS , Feb. 11, 2016  Attending ... but for those with type 1 diabetes, the journey ... juggle class schedules, assignments and campus activities, they also ... diabetes. On top of that, many are living away ... Scholars Foundation (Foundation) Lilly Diabetes Tomorrow,s Leaders Scholarship ...
Breaking Medicine Technology: