Substantial Histone Reduction Modulates Genome-wide Nucleosomal Occupancy and Global Transcriptional Output

The recent wave of publications seem to continue, and another paper just appeared in PLoS Biology. Like the previous one, this one was in the reviewing rounds for very long, and so we are very happy that it finally appeared.

This project is a collaboration with the group of Alessandra Agresti and Marco Bianchi from San Raffaele University in Milan. They are part of a European consortium that we are also members of, and they approached us to get help on dealing with nucleosome organization. Assaf got involved, into what was dubbed "The Italian Job" in lab meeting. After almost two years, the result is an impressive article.

To summarize the basic idea, the experiments by Barbara Celona, the main author, and other member's of the Milan group show that deletion in a key gene reduces the number of nucleosomes in the genome. As a result the DNA strands are packed by smaller number of nucleosomes. By mapping the locations of these nucleosomes we can see if nucleosome reduction leads to uniform change in density, or preferential reduction at particular locations, and what is the effect on transcription.

Source: PLoS Biology Synopsis by Robin Mejia

Our results show that nucleosome loss is mostly in locations that are less packed in normal cells, and moreover, that this loss correlates with increased transcription.

Cool!

Presidential Conference

This week we participated in the Israeli President's annual conference. This is a the place where important people from Israel and abroad come to talk about the future of the country, the region, and the world.

The Hebrew University was a co-sponsor of the event, and had its own space to presents research highlight. The target audience was not scientifically minded, so the message was to be kept at high level. Each participating lab had a small space where a large poster was presented on a table. We had TV monitors showing a movie about our lab.

Assaf and Avital participated as guides, and got to see the important people and even to talk with few. We did manage to get to hear some of the sessions, although I suspect the main action at these events in beyond the scenes.

The Comeback + Visitors

About three months ago Moran went off on a maternity leave. Today was the official first step on returning to academic work. To make the transition easier she was accompanied by her family. We got a chance to meet the family and the joy young ones bring.

Another weekend diving

Two weekend days to enjoy diving in Eilat. Many good sights and nice company of local people and fellow divers.

Patterns and Mechanisms of Ancestral Histone Protein Inheritance in Budding Yeast

Hot from the (virtual) press! A paper that we have been working on for almost a year appeared today in PLoS Biology. This is three way collaboration between Fred van Leeuwen's group at the Netherlands Cancer Institute, Ollie Rando's group at UMass Medical School and our group. The work on our end was mostly Assaf's who is a co-first author. 

The interesting aspect of this paper is that using a trick developed in Fred's group, they can switch a "tag" on a histone H3 protein. This means that up to a certain point all H3 proteins are tagged by one tag, and after the switch they are all tagged with a different tag. Using this switch we can find out where these "old" histones are several generations after the switch. This gives us insight on how the cells perserve old histones during several cycles of replication.

To quote ourselves:

To our surprise, ancestral histones accumulate near the 5′ end of long, relatively inactive genes. Using a mathematical model, we show that our results can be explained by the combined effects of histone replacement, histone movement along genes from 3′ towards 5′ ends, and histone spreading during replication. Our results show that old histones do move but stay relatively close to their original location (within around 400 base-pairs), which places important constraints on how chromatin could potentially carry epigenetic information. Our findings also suggest that accumulation of the ancestral histones that are inherited can influence histone modification patterns.

To get to these conclusions Assaf implemented a mathematical model that takes into account the processes that affect nucleosome positions, and then showed that this model can provide a good fit to the data if we consider turnover, passback of nucleosomes (from 3' to 5'), and localized dispersion during replication.  

Freiburg/Heidelberg

Just returned from a week long trip to Germany. It started by a visit to Max Planck Institute for Immunobiology and Epigenetics at Freiburg to attend a one day workshop on Chromatin. After the talks the hosts took us to a nice resto-bar where there was a long and lively scientific discussion over beer, schnitzel and white asparagus.

The next morning, it was raining, but I went on a brief walk in Frieburg's old town.

Afterwards, I continued to Heidelberg to attend the EMBL Chromatin and Epigenetics meeting. This was a four and half day meeting with a lot of interesting talks and  discussions with people. 

The meeting was held in an impressive new training center at EMBL's campus on the hills above Heidelberg. It is built as a double helix, and so there are no floors, but rather helical ramp ways all around.

I also took a half day off to go bike riding in the area and had few hours to visit the famous Schloss.

Another graduation and a new lab website

Last week Noa officially graduated. She turned in her dissertation on "Transcription Regulation Models and Their Application to Human Disease Research". She is moving on to the Weizmann Institute to work with Yaqub Hanna. 

As a parting gift before leaving us to the Weizmann, Noa created a new website for the lab (we were missing one for too long).

We will have a proper sendoff for Noa soon, although the scheduling of the event seem to be a serious challenge.