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#chromatin modifications

2 public questions tagged with this topic.

Stem Cell -lll

Which of the following chromatin modifications is associated with differentiation?

Differentiation involves stable shutdown of stemness genes and activation of lineage-specific programs through coordinated chromatin remodeling processes. Histone acetylation by p300 and CBP opens embryonic enhancers to allow transcription, while subsequent deacetylation and H3K27 trimethylation via PRC2 polycomb complex closes pluripotency loci. DNA methylation by DNMT3A and DNMT3B at Oct4 and Nanog promoters locks commitment irreversibly. Heterochromatin protein 1-mediated heterochromatin formation silences repetitive elements and alternative lineages. All these modifications including acetylation changes, methylation patterning, and repressive compaction collectively drive progressive developmental restriction effectively.

Ref: Bernstein et al., Cell 2006; Meshorer & Misteli, Nat Rev Mol Cell Biol 2006: Chromatin modifications differentiation.

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Regulation of chromatin structure

Which histone variant is linked with inactive X chromosome?

Histone variants mark chromosome-wide silencing programs. While macroH2A is best characterized for Barr body enrichment, ubiquitylated forms of H2A.Z have been detected on facultative heterochromatin of inactive X in female mammalian cells, colocalizing with H3K27me3, loss of H4 acetylation and DNA methylation. This variant participates in dynamic relocalization of HP1 and establishment of facultative heterochromatin post-meiosis, replacing macroH2A at certain developmental stages. Its presence reflects context-dependent roles beyond active promoters, contributing to stable propagation of X-chromosome inactivation through recruitment of PRC2 and transcriptional repressor complexes.

Ref: Sarcinella et al., Nature, H2A.Z Ubiquitylation Enriched on Inactive X Chromosome, Facultative Heterochromatin

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