LOW-LEVEL REPRESSIVE HISTONE MARKS FINE-TUNE GENE TRANSCRIPTION IN NEURAL STEM CELLS

Low-level repressive histone marks fine-tune gene transcription in neural stem cells

Low-level repressive histone marks fine-tune gene transcription in neural stem cells

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Coordinated regulation of gene activity by transcriptional and translational mechanisms poise stem cells for a timely cell-state transition during differentiation.Although important for all stemness-to-differentiation transitions, mechanistic understanding of the Telephone Accessories fine-tuning of gene transcription is lacking due to the compensatory effect of translational control.We used intermediate neural progenitor (INP) identity commitment to define the mechanisms that fine-tune stemness gene transcription in fly neural stem cells (neuroblasts).We demonstrate that the transcription factor FruitlessC (FruC) binds cis-regulatory elements of most genes uniquely transcribed in neuroblasts.

Loss of fruC function alone has no effect on INP commitment but drives INP dedifferentiation Lacrosse - Shoes when translational control is reduced.FruC negatively regulates gene expression by promoting low-level enrichment of the repressive histone mark H3K27me3 in gene cis-regulatory regions.Identical to fruC loss-of-function, reducing Polycomb Repressive Complex 2 activity increases stemness gene activity.We propose low-level H3K27me3 enrichment fine-tunes gene transcription in stem cells, a mechanism likely conserved from flies to humans.

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