Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin Journal Article
| Authors: | Vaquero, A.; Scher, M.; Lee, D.; Erdjument-Bromage, H.; Tempst, P.; Reinberg, D. |
| Article Title: | Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin |
| Abstract: | We characterized human SirT1, one of the human homologs of the budding yeast Sir2p, an NAD+-dependent histone deacetylase involved in establishing repressive chromatin and increased life span. SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. RNAi-mediated decreased expression of SirT1 in human cells causes hyperacetylation of H4-K16 and H3-K9 in vivo. SirT1 interacts with and deacetylates histone H1 at lysine 26. Using an inducible system directing expression of SirT1 fused to the Gal4-DNA binding domain and a Gal4-reporter integrated in euchromatin, Gal4-SirT1 expression resulted in the deacetylation of H4-K16 and H3-K9, recruitment of H1 within the promoter vicinity, drastically reduced reporter expression, and loss of H3-K79 methylation, a mark restricting silenced chromatin. We propose a model for SirT1-mediated heterochromatin formation that includes deacetylation of histone tails, recruitment and deacetylation of histone H1, and spreading of hypomethylated H3-K79 with resultant silencing. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; methylation; protein; protein interaction; rna; gene expression regulation; chromatin; cell nucleus; gene silencing; yeast; saccharomycetales; dna binding; histones; histone deacetylases; nad; lysine; histone deacetylase; deacetylation; heterochromatin; nicotinamide adenine dinucleotide; acetylation; transcription factor gal4; histone h4; polypeptide; promoter regions (genetics); histone h1; sirtuins; humans; human; article; sirt1 protein |
| Journal Title: | Molecular Cell |
| Volume: | 16 |
| Issue: | 1 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2004-10-08 |
| Start Page: | 93 |
| End Page: | 105 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2004.08.031 |
| PROVIDER: | scopus |
| PUBMED: | 15469825 |
| DOI/URL: | |
| Notes: | Mol. Cell -- Cited By (since 1996):354 -- Export Date: 16 June 2014 -- CODEN: MOCEF -- Source: Scopus |
