Nucleosome remodeler exclusion by histone deacetylation enforces heterochromatic silencing and epigenetic inheritance - presented by Dr Rakesh Kumar Sahu

Nucleosome remodeler exclusion by histone deacetylation enforces heterochromatic silencing and epigenetic inheritance

Dr Rakesh Kumar Sahu

Dr Rakesh Kumar Sahu

Associated Molecular Cell article

R. K. Sahu et al. (2024) Nucleosome remodeler exclusion by histone deacetylation enforces heterochromatic silencing and epigenetic inheritance. Molecular Cell
Article of record
Nucleosome remodeler exclusion by histone deacetylation enforces heterochromatic silencing and epigenetic inheritance
Dr Rakesh Kumar Sahu
Rakesh Kumar Sahu
National Cancer Institute and National Institutes of Health

Heterochromatin enforces transcriptional gene silencing and can be epigenetically inherited, but the underlying mechanisms remain unclear. Here, we show that histone deacetylation, a conserved feature of heterochromatin domains, blocks SWI/SNF subfamily remodelers involved in chromatin unraveling, thereby stabilizing modified nucleosomes that preserve gene silencing. Histone hyperacetylation, resulting from either the loss of histone deacetylase (HDAC) activity or the direct targeting of a histone acetyltransferase to heterochromatin, permits remodeler access, leading to silencing defects. The requirement for HDAC in heterochromatin silencing can be bypassed by impeding SWI/SNF activity. Highlighting the crucial role of remodelers, merely targeting SWI/SNF to heterochromatin, even in cells with functional HDAC, increases nucleosome turnover, causing defective gene silencing and compromised epigenetic inheritance. This study elucidates a fundamental mechanism whereby histone hypoacetylation, maintained by high HDAC levels in heterochromatic regions, ensures stable gene silencing and epigenetic inheritance, providing insights into genome regulatory mechanisms relevant to human diseases.

References
  • 1.
    R. K. Sahu et al. (2024) Nucleosome remodeler exclusion by histone deacetylation enforces heterochromatic silencing and epigenetic inheritance. Molecular Cell
National Institutes of Health logo
Intramural Fellows Unveiling Scientific Excellence (InFUSE)
National Institutes of Health (National Cancer Institute)
Cite as
R. Kumar Sahu (2024, November 14), Nucleosome remodeler exclusion by histone deacetylation enforces heterochromatic silencing and epigenetic inheritance
Share
Details
Listed seminar This seminar is open to all
Recorded Available to all
Video length 12:23
Q&A Now closed