Friday, May 25, 2018 | ePaper

Key factor identified in gene silencing

  • Print


Life Desk :
A fertilized human egg develops into multiple tissues, organs and about 200 distinct cell types. Each cell type has the same genes, but they are expressed differently during development and in mature cells.
Understanding the mechanisms that turn sets of genes on or off is a fundamental quest in biology, and one that has clinical importance in diseases like cancer, where gene control goes awry.
'The stable nucleosome array leads to a chromatin architecture that is refractory to further remodeling required for ubiquitinated-H2A target gene activation.'
University of Alabama at Birmingham researcher Hengbin Wang, Ph.D., and colleagues have identified one such mechanism. In a paper published this week in Proceedings of the National Academy of Sciences, Wang and colleagues describe a key role for a protein called RSF1 in silencing genes.
Besides the molecular biology details, the researchers also showed that disruption of RSF1 expression in the embryos of African clawed frogs caused severe developmental defects in the tadpoles through a dysregulation of mesodermal cell fate specification. RSF1 acts on chromatin, the organized structure of the chromosome where the 6-foot-long DNA of each human cell is highly condensed by wrapping around spools of histone proteins. Chromatin is not static, however it is highly dynamic and changes in its structure to control different physiological processes.
One contributor to chromatin fluidity is modifications of the histone proteins made by adding or removing chemical groups to the histone tails. The histones can be modified by acetylation, phosphorylation, methylation, ubiquitination or ADP-ribosylation.
In his current work, Wang, an associate professor of biochemistry and molecular genetics in the UAB School of Medicine, focused on the addition of ubiquitin to the histone subunit H2A. This prevalent modification is linked to gene silencing, and removal of ubiquitin from H2A leads to gene activation. Wang and colleagues discovered that RSF1 mediates the gene-silencing function of ubiquitinated-H2A.
They found that RSF1 -- which stands for remodeling and spacing factor 1, a subunit of the RSF complex is a ubiquitinated-H2A binding protein that reads ubiquitinated-H2A through a previously uncharacterized and obligatory ubiquitinated-H2A binding domain.
In human and mouse cells, the genes regulated by RSF1 were found to overlap significantly with those controlled by part of a complex that ubiquitinates H2A. Knockout of RSF1 in cells derepressed the genes regulated by RSF1, and this was accompanied by changes in ubiquitinated-H2A chromatin organization and release of linker histone H1.
In the paper, Wang and colleagues proposed a model for the action of RSF1 in gene silencing.
"RSF1 binds to ubiquitinated-H2A nucleosomes to establish and maintain the stable ubiquitinated-H2A nucleosome pattern at promoter regions," they wrote.
"The stable nucleosome array leads to a chromatin architecture that is refractory to further remodeling required for ubiquitinated-H2A target gene activation. When RSF1 is knocked out, ubiquitinated-H2A nucleosome patterns are disturbed and nucleosomes become less stable, despite the presence of ubiquitinated-H2A. These ubiquitinated-H2A nucleosomes are subjected to chromatin remodeling for gene activation."
Wang says knowledge of the ubiquitinated-H2A binding site may help in the discovery of other ubiquitinated histone-binding proteins.
Source: Eurekalert

More News For this Category

Jewellery to buy for daughters

Jewellery to buy for daughters

Life Desk :Few ideas to buy jewelries:· Material: Daughters and brides of this age have ditched the old jewellery trend of buying gold. They prefer more of silver lining

Suffocating oceans creating dead zones

Suffocating oceans creating dead zones

Life Desk :Our seas and oceans are gasping for breath with very little oxygen in huge pockets of water.A new study by University of East Anglia researchers confirms the

For an ideal kitchen

For an ideal kitchen

Life Desk :The kitchen is undeniably one of the most important rooms in a home as it is the area where the family congregates, meals are prepared, and guests

Access to quality healthcare

Dr. Samir Kumar Saha  :(From previous issue)The gap between what the government has assessed  (sanctioned) as requirement for providing  healthcare services and the positions vacant clearly shows that Bangladesh

Make healthcare affordable for all

Sania Nishtar  :Half of the planet cannot access essential health services. For many people, paying to see a doctor, obtaining medications, seeking family-planning advice, or even getting immunized against

Calculated risks in life

Jay L. Zagorsky :Risk is everywhere and associated with everything. For example, the Centers for Disease Control and Prevention a decade ago estimated over 20 million people a year

Int'l edn confce ends

Int'l edn confce ends

A three-day international education conference ended in Canada on Saturday. Al Amin and Bapan Saha, two officials of SA Associates, a renowned education and immigration consulting firm, attended the

Access to quality health care

Access to quality health care

Dr. Samir Kumar Saha  :World Health Day (WHD) is celebrated across the world, including in Bangladesh, every year on April 7 under the leadership of World Health Organization (WHO).

Post it, don't expect FB to protect your rights

Post it, don't expect FB to protect your rights

Sarah Joseph :Facebook has had a few bad weeks. The social media giant had to apologise for failing to protect the personal data of millions of users from being accessed

Sleep apnea patients may not always need specialists

Sleep apnea patients may not always need specialists

Lisa Rapaport :Some patients with a common nighttime breathing disorder known as obstructive sleep apnea may do just as well at managing the condition when they see a primary