A good actor can play very different roles and still make you believe in the character. For example, who knew Wolverine could emote and sing, like Hugh Jackman does in Les Misérables? Just the same, it turns out that MeCP2, a protein thought to repress transcription by binding to 5mC (5-methylcytosine, actually seems to encourage transcription in the brain by binding to 5hmC (5-hydroxymethylcytosines).
The New York and U.K. researchers (who originally found 5hmC in neurons in 2009) wanted to dig into what 5hmC was doing in the brain. Sure, it’s also in embryonic stem cells, but there’s so much more of it (10 times more) in neurons. What gives?
They studied three types of neurons and looked at how 5hmC and 5mC related to gene expression. Here’s what they learned:
- 5hmC is enriched in actively transcribed genes, whereas 5mC is enriched in less active genes. 5hmC was high in gene bodies, and 5mC was high at promoters.
- But the exact relationship between cytosine modification status and gene expression varied among the cell types they studied.
- Surprisingly, MeCP2 bound to both 5hmC and 5mC, not just preferentially to 5mC as previous studies suggested.
- A mutation of MeCP2 implicated in Rett syndrome, a developmental disorder mostly affecting girls, reduced MeCP2 binding to 5hmC, but not to 5mC.
- Although previous studies suggested that MeCP2 binding to 5mC represses transcription, this study shows that in the brain, MeCP2 plays a role in helping transcription happen. This is likely through its binding to 5hmC.
“These findings support a model in which 5hmC and MeCP2 constitute a cell-specific epigenetic mechanism for regulation of chromatin structure and gene expression,” say the researchers.
Read all the info at Cell, December 2012.