Featured Research

from universities, journals, and other organizations

Study shows how bookmarking genes pre-cell division hastens their subsequent reactivation

Date:
October 10, 2011
Source:
Cold Spring Harbor Laboratory
Summary:
By observing and measuring the kinetics of activation of a single gene locus in a cell before it divides and comparing it with the same gene's reactivation in newly formed daughter cells, scientists have discovered how how bookmarking a gene pre-division causes it to get reactivated post-division.

In order for cells of different types to maintain their identities even after repeated rounds of cell division, each cell must "remember" which genes were active before division and pass along that memory to its daughter cells. Cells deal with this challenge by deploying a "bookmarking" process. In the same way a sticky note marks the last-read page in a book, certain molecules tag the active genes in a cell so that, after it divides, the same genes are reactivated right away in the new cells.

Related Articles


"What we didn't know, however, was how bookmarking a gene pre-division causes it to get reactivated post-division," says CSHL Professor David L. Spector, Ph.D. By observing and measuring the kinetics of activation of a single gene locus -- the specific chromosomal location of a gene -- in a cell before it divides and comparing it with the same gene's reactivation in newly formed daughter cells, Spector and his team have now arrived at the answer to this question. Their study appears online in Nature Cell Biology on October 9.

During cell division, or mitosis, there is a temporary blackout of all gene activity within the cell. The cell's chromatin -- the coils of chromosomal DNA wrapped around histones (proteins that package DNA) -- becomes tightly compacted; most proteins that normally cling to chromatin to maintain gene expression are stripped away; and transcription -- the copying of DNA into RNA -- comes to a halt. When division ends, the chromatin in the new cells de-compacts or relaxes, transcription-regulating proteins are recruited to specific sites in the chromatin and gene transcription begins anew.

To find out how this post-division process is set in motion, Spector's team used an innovative live cell imaging approach that they previously developed to make real-time observations of a specific gene locus and the RNA transcribed from the locus when it is activated. In this experimental system, the gene locus under observation, the transcription-activating protein, and the RNA produced by the gene are each labeled with a different colored fluorescent tag.

"By looking at gene expression at the same locus (a gene's position on the chromosome) at two different times -- during 'interphase,' which is the stage between cell division, and after mitosis, we discovered that the gene is activated much more rapidly when it is reactivated post-mitosis," explains Spector. Further analysis suggested that the transcriptional activity during interphase leaves behind a memory in the form of a bookmark that is preserved during mitosis and is crucial for the rapid post-mitotic reactivation of the gene.

This bookmark, the scientists show, is a histone molecule that has undergone a chemical modification called acetylation, which alters its interactions with DNA as well as with proteins that bind to it. "We observed that the gene locus accumulates this acetylated histone, called H4K5Ac, prior to mitosis. During mitosis, H4K5Ac stays in place along with a small amount of another protein called BRD4, which keeps the locus less tightly packed than the rest of the chromatin," explains the paper's first author Rui Zhao, Ph.D.

When mitosis ends, the scientists observed additional BRD4 being rapidly recruited to the bookmarked loci in the daughter cells. This in turn loosens up the tightly wound chromatin and recruits other members of the transcription machinery to the bookmarked gene, which is then rapidly reactivated.

Previous studies have shown BRD4 to be a "reader" of chromatin marks such as acetylated histones, which might contribute to its quick buildup at the bookmarked loci, according to Spector. Another recent CSHL study identified a role for BRD4 in cancer cell proliferation, showing that inhibiting its activity stopped leukemia progression.

"Our study points to a new role for BRD4 in chromatin decompaction," says Spector. "The fact that BRD4 recruitment precedes the arrival of RNA polymerase II at the bookmarked loci in post-mitotic cells suggests a more global role for this protein in gene reactivation in newly formed cells," he adds. "It's clear that the 'early-to-activate' genes are the ones that need to be bookmarked and there will be many different bookmarks. We are now trying to identify these genes and determine what regulates their selection for early reactivation."

This work was supported by a grant from the NIH/NIGMS (42694).


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. Rui Zhao, Tetsuya Nakamura, Yu Fu, Zsolt Lazar and David L. Spector. Gene bookmarking accelerates the kinetics of post-mitotic transcriptional reactivation. Nature Cell Biology, October 9, 2011 DOI: 10.1038/ncb2341

Cite This Page:

Cold Spring Harbor Laboratory. "Study shows how bookmarking genes pre-cell division hastens their subsequent reactivation." ScienceDaily. ScienceDaily, 10 October 2011. <www.sciencedaily.com/releases/2011/10/111009140157.htm>.
Cold Spring Harbor Laboratory. (2011, October 10). Study shows how bookmarking genes pre-cell division hastens their subsequent reactivation. ScienceDaily. Retrieved November 22, 2014 from www.sciencedaily.com/releases/2011/10/111009140157.htm
Cold Spring Harbor Laboratory. "Study shows how bookmarking genes pre-cell division hastens their subsequent reactivation." ScienceDaily. www.sciencedaily.com/releases/2011/10/111009140157.htm (accessed November 22, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Saturday, November 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Anglerfish Rarely Seen In Its Habitat Will Haunt You

Anglerfish Rarely Seen In Its Habitat Will Haunt You

Newsy (Nov. 22, 2014) For the first time Monterey Bay Aquarium recorded a video of the elusive, creepy and rarely seen anglerfish. Video provided by Newsy
Powered by NewsLook.com
Birds Around the World Take Flight

Birds Around the World Take Flight

Reuters - Light News Video Online (Nov. 22, 2014) An imperial eagle equipped with a camera spreads its wings over London. It's just one of the many birds making headlines in this week's "animal roundup". Jillian Kitchener reports. Video provided by Reuters
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Raw: Baby Okapi Born at Houston Zoo

Raw: Baby Okapi Born at Houston Zoo

AP (Nov. 20, 2014) The Houston Zoo released video of a male baby okapi. Okapis, also known as the "forest giraffe", are native to the Democratic Republic of the Congo in Central Africa. Video is mute from source. (Nov. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins