G1 length dictates H3K27me3 landscapes

Area of Science:

• Epigenetics
• Cell Biology
• Developmental Biology

Background:

• Stem cells exhibit lower facultative heterochromatin (H3K27me3) than differentiated cells.
• Mechanisms controlling differential H3K27me3 levels between stem and differentiated cells are not fully understood.

Purpose of the Study:

• To investigate the role of cell cycle length in regulating H3K27me3 levels in stem cells.
• To test the hypothesis that a fast cell cycle restricts H3K27me3 in stem cells.

Main Methods:

• Mouse embryonic stem cells (mESCs) were subjected to G1 phase lengthening using thymidine block or 2i medium.
• Changes in H3K27me3 levels were analyzed globally and at specific loci using CUT&RUN and ChIP-seq.
• G1 shortening was induced in differentiated cells to observe inverse effects.

Main Results:

• Lengthening the G1 phase in mESCs increased H3K27me3 levels, both globally and at specific loci.
• Regions gaining H3K27me3 during G1 arrest and 2i media treatment showed overlap.
• Shortening G1 in differentiated cells led to decreased H3K27me3.
• G1 lengthening restored H3K27me3 in tumor cells with H3K27M mutation.

Conclusions:

• Cell cycle G1 phase length is a critical regulator of H3K27me3 landscapes.
• Cell cycle duration influences stem cell epigenome and cellular identity.
• G1 length is an essential determinant of H3K27me3 across diverse cell types.