Most of us understand the importance of a good neighborhood; we look for somewhere to reflect our identity and to bring us together with similar minded people. Interestingly, recent work from the labs of Keji Zhao and Richard A. Young suggests that certain genes in embryonic stem cells (ESCs) act in a similar manner.
The inquisitive crew of researchers wanted to take a closer look at the structural elements in key genes involved in pluripotency, so they used ChIA-PET (Chromatin Interaction Analysis by Paired-End Tag Sequencing), to get an in depth view of genome-wide long range chromatin interactions.
When the data crunching dust settled, the team found that chromosomal regions that contain pluripotency promoting ESC-associated genes loop together into the same nuclear “neighborhood” in regions where they can be freely expressed and give the cell its pluripotent identity. Likewise, genes not expressed in ESCs loop together into “silent” nuclear regions, where they become silenced.
Now, if it was only that easy to silence your neighbours during those obnoxious karaoke parties….
Getting a bit more into the details, here are a few highlights of their approach/findings:
- They used a modified chromatin IP technique known as ChIA-PET to assess chromosome structures associated with active and silent genes
- They integrated their analysis with chromatin modification and gene expression patterns
- This produced a genome wide map of the interactions between the enhancer-promoter elements which control gene expression
- From this, they found that neighbourhoods are formed by the interaction of two CTCF transcription factor binding sites and the protein cohesin, generating chromosome loops
- Importantly, they associated “active” loops with genes that give ESCs their identity
Interestingly, just like the arrival of bad neighbors next door can play havoc with your life, the researchers also demonstrated that the disruption of chromosomal looping in ESCs led to the partial loss of their cellular identity. Therefore, both at home and in the ESC nuclei, it’s important to have just the right neighborhood.
Check out the details at Cell, 2014