Tuesday, June 7, 2011

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.  

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