Although we often think of human embryonic stem cell (hESC) lines as being pretty much the same (kind of like the Kardashian sisters), they really are different according to a report by UCLA researchers. Even though they usually can differentiate into the same cell types, hESCs have different methylation patterns—and that may affect gene expression.
Using genome-wide bisulfite sequencing (BS-seq), the researchers compared global methylation and expression levels in three hESCs: HSF1, H1, and H9 (aka WA09). Here’s what they saw:
- Between 1.4% and 2% of the genomes varied in methylation. The common sites of differential methylation were mostly in exons and CpG islands.
- For the first time, they show that highly methylated non-CG sites are rare but strongly conserved across hESC lines (especially when in TACAG sequences) and these are enriched in genes and splice sites.
In a new strategy, the researchers combined the BS-seq data with RNA-seq data and found:
- 1020 genes expressed preferentially from one allele vs. the other.
- About 14% of all GC sites had differential methylation on the two chromosomes.
- Six genes had both differential methylation and allele expression, suggesting that methylation had something to do with expression.
- Methylation at the binding sites of several transcription factors was correlated with expression, so methylation may affect whether a transcription factor binds in its predicted spot.
See if you can tell the hESC lines apart at Genome Biology, July 2011.