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The See-saw of Differentiation: Tipping the Chromatin Balance

Laboratory of Cancer Prevention, SAIC-FCRDC, National Cancer Institute, Frederick, MD 21701

SUMMARY

Histone modifications, specifically, methylation of lysine residues in histone 3 (H3), determine chromatin structure and accessibility for transcription. A recent study by Bernstein and Lander identified a unique pattern of H3 methylation at the promoter region of developmental genes in pluripotent stem cells. The pattern consists of the simultaneous presence of a silencing mark [methylation of Lys²⁷ on H3 (H3K27me)] and an activation mark (H3K4me). This bivalent mark seems associated with a poised state of transcription and resolves upon differentiation largely into either H3K27me or H3K4me. Skin fibroblasts that can be reverted in culture to the pluripotent stage show re-establishment of the bivalent chromatin pattern. This switch in chromatin states may be key to our understanding of developmental and tissue specific regulation of gene expression and may be therapeutically useful in regenerative medicine.