Seven years ago, Dr. Joe Gall of the Carnegie Institute in Baltimore, Md. and coworkers noticed an aggregation of molecules along a a block of genome that codes for the critical histones, but they had no idea how this aggregate or "histone locus body" was formed.
This is a micrograph of a nuclei from a fruit fly salivary gland showing the endogenous histone locus body (large arrow) and HLB formed on the inserted histone genes (small arrow).
Credit: Deirdre Tatomer, UNC Dept. of Biology.
Now, research conducted in fruit flies at the University of North Carolina School of Medicine has pinpointed a specific DNA sequence that both triggers the formation of this "histone locus body" and turns on all the histone genes in the entire block.
The finding, published March 25, 2013 in the journal Developmental Cell, provides a model for the coordinated synthesis of histones needed for assembly into chromatin, a process critical to keeping chromosomes intact and passing genetic information from generation to generation.
"Our study has uncovered a new relationship between nuclear architecture and gene activity," said senior study author Bob Duronio, PhD, professor of biology and genetics at UNC. "In order to make chromosomes properly, you need to make these histone building blocks at the right time and in the right amount. We found that the cell has evolved this complex architecture to do that properly, and that involves an interface between the assembly of various components and the turning on of a number of genes."
In the fruit fly, as in the human, the five different histone genes exist in one long chunk of the genome. The "histone locus" in flies contains 100 copies of each of the five genes, encompassing approximately 500,000 nucleotides of A's, C's, T's and G's. The proteins required for making the histone message – a process that must happen every time a new strand of DNA is copied – come together at this "histone locus" to form the "histone locus body."
Duronio and co-senior study author William Marzluff, PhD, Kenan Distinguished Professor of Biochemistry and Biophysics, wanted to figure out how these factors knew to meet at the histone locus.
They inserted different combinations of the five histone genes into another site of the genome, and looked to see which combinations recruited a new histone locus body. The researchers found that combinations that contained a specific 300 nucleotide sequence – the region between the H3 and H4 histone genes – formed a histone locus body. In contrast, combinations of genes that lacked this sequence did not form the body. They went on to show that this sequence turned on not only the H3 and H4 genes in its direct vicinity, but also other histone genes in the block.
Though the research was conducted entirely in fruit flies, it may lend insight into mechanisms that keep the genome from becoming unstable – and causing early death or illness -- in higher organisms.
"Humans and flies have these very same histone genes. They have the same proteins in the histone locus body. So understanding precisely how this works in flies will help us understand cell division in humans," said Marzluff.
The research was funded by the National Institute of General Medical Sciences, National Institutes of Health. Study co-authors from UNC include Harmony R. Salzler, Deirdre C. Tatomer, Pamela Y. Malek, Stephen L. McDaniel, and Anna N. Orlando.
Les Lang | EurekAlert!
Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University
Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
25.04.2017 | Physics and Astronomy
25.04.2017 | Materials Sciences
25.04.2017 | Life Sciences