Biomedical Engineering Reference
In-Depth Information
Fig. 2 (a)Number of common targets of multiple factors. y-axis represents the number of
target promoters occupied by transcription factor(s). Red dots represent the accumulated
number of target promoters. (b) GSEA (gene-set enrichment analysis) showing the relation-
ship between target gene expression and factor occupancy. Target promoters were classified
based on the number of co-occupying factors and corresponding gene expression upon
differentiation was tested. Common targets of six factors are enriched in active genes in ES
cells, whereas single-factor-only targets are more repressed. (c) Left panel: H3K4me3 (red
line) and H3K27me3 (blue line) status for Myc target promoters. Right panel: Expression
profiles of Myc target genes at different time points upon differentiation (0-18 hr: red, 4-14
days: blue). Total 6632 target genes of any of nine factors are shown, and moving window
average (bin size 50 and step size 1) was applied (b and c). (d) GSEA analyses showing single-
factor Nanog and Oct4 which target more repressed genes, whereas myc alone targets active
genes
occupancy reflects broad changes in chromatin accessibility. Such widespread
effects may account in part for the potency of c-myc as a facilitator of somatic
cell reprogramming. Among the four ''Yamanaka'' factors, Klf4 may serve in
part as an upstream regulator of feed-forward circuits involving Oct4 and Sox2,
as well as downstream effectors (e.g., Nanog). Based on the promoter occu-
pancy studies, Klf4 may also regulate c-myc, which itself participates in a feed-
forward circuit favoring cell proliferation and chromosome accessibility
(Fig. 3). Ng's group in Singapore used ChIP-seq methods with extended 13
transcription factors (Nanog, Oct4, Sox2, Klf4, c-myc, CTCF, Tcfc2I1, n-myc,
Smad1, STAT3, Zfx, E2f1, Esrrb) including core factors and reprogramming
