Rb targets histone H3 methylation and HP1 to promoters

  title={Rb targets histone H3 methylation and HP1 to promoters},
  author={S{\o}ren Jensby Nielsen and Robert Schneider and Uta-Maria Bauer and Andrew J. Bannister and Ashby J. Morrison and D{\'o}nal O’Carroll and Ron Firestein and Michael L. Cleary and Thomas Jenuwein and Rafael E. Herrera and Tony Kouzarides},
In eukaryotic cells the histone methylase SUV39H1 and the methyl-lysine binding protein HP1 functionally interact to repress transcription at heterochromatic sites. Lysine 9 of histone H3 is methylated by SUV39H1 (ref. 2), creating a binding site for the chromo domain of HP1 (refs 3, 4). Here we show that SUV39H1 and HP1 are both involved in the repressive functions of the retinoblastoma (Rb) protein. Rb associates with SUV39H1 and HP1 in vivo by means of its pocket domain. SUV39H1 cooperates… 

Functional and physical interaction between the histone methyl transferase Suv39H1 and histone deacetylases.

The results suggest that a complex containing both the Suv39H1 histone methyl transferase and histone deacetylases could be involved in heterochromatin silencing or transcriptional repression by Rb.

Balance between Acetylation and Methylation of Histone H3 Lysine 9 on the E2F-Responsive Dihydrofolate Reductase Promoter

The results indicate that the temporal regulation of euchromatic promoters may involve controlling the balance between methylation and acetylation of histone H3 lysine 9, a feature previously described for the spatial regulation of chromatin function.

Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin

Observations indicate that the RB1 family is involved in maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin, linking tumour suppression and the epigenetic definition of chromatin.

Relationship between Histone H3 Lysine 9 Methylation, Transcription Repression, and Heterochromatin Protein 1 Recruitment

Comparisons of the effects of tethering two H3-K9-specific histone methyltransferases to chromatin on transcription and HP1 recruitment indicate that H2K9 methylation alone can suppress transcription but is insufficient forHP1 recruitment in the context of chromatin, exemplifying the importance of Chromatin-associated factors in reading the histone code.

L3MBTL1, a Histone-Methylation-Dependent Chromatin Lock

The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase.

The data show a direct connection between the enzymes responsible for DNA methylation and histone methylation, and substantiate the notion of a self-reinforcing repressive chromatin state through the interplay between these two global epigenetic modifications.

Methyl-CpG Binding Domain 1 (MBD1) Interacts with the Suv39h1-HP1 Heterochromatic Complex for DNA Methylation-based Transcriptional Repression*

Data indicate that MBD1 may tether the Suv39h1-HP1 complex to methylated DNA regions, suggesting the presence of a pathway from DNA methylation to the modifications of histones for epigenetic gene regulation.

Tethering of HP1 proteins to chromatin is relieved by phosphoacetylation of histone H3

In vivo phosphorylation of serine 10 in G2 can occur on histone tails methylated on lysine 9, and it is proposed that phosphoacetylation of histone H3 could be a general mechanism allowing the cell to overcome HP1‐mediated transcriptional repression.

Interaction of HP1 and Brg1/Brm with the Globular Domain of Histone H3 Is Required for HP1-Mediated Repression

The data suggest that HP1 chromoshadow-domains can benefit from the opening of nucleosomal structures to bind chromatin and thatHP1 proteins use this property to detect and arrest unwanted chromatin remodeling.



Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain

A stepwise model for the formation of a transcriptionally silent heterochromatin is provided: SUV39H1 places a ‘methyl marker’ on histone H3, which is then recognized by HP1 through its chromo domain, which may also explain the stable inheritance of theheterochromatic state.

Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins

It is shown that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases) generate a binding site for HP1 proteins—a family of heterochromatic adaptor molecules implicated in both gene silencing and supra-nucleosomal chromatin structure.

Retinoblastoma protein recruits histone deacetylase to repress transcription

It is shown that Rb associates with a histone deacetylase, HDAC1, through the Rb ‘pocket’ domain, and that active transcriptional repression by Rb may involve the modification of chromatin structure.

Retinoblastoma protein represses transcription by recruiting a histone deacetylase

It is shown here that the histone deacetylase HDAC1 physically interacts and cooperates with Rb, and that the Rb/HDAC1 complex is a key element in the control of cell proliferation and differentiation and that it is a likely target for transforming viruses.

Regulation of chromatin structure by site-specific histone H3 methyltransferases

A functional interdependence of site-specific H3 tail modifications is revealed and a dynamic mechanism for the regulation of higher-order chromatin is suggested.

Interaction with members of the heterochromatin protein 1 (HP1) family and histone deacetylation are differentially involved in transcriptional silencing by members of the TIF1 family

An association of TIF1β with both heterochromatin and euchromatin in interphase nuclei is reported and it is shown that trichostatin A, an inhibitor of histone deacetylases, can interfere with both Tif1 and HP1 silencing.

Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog ofDrosophila Su(var)3-9

A phosphorylation-dependent mechanism for regulating the chromatin organizing activity of a mammalian su(var) protein is suggested and the SET domain is implicate as a gatekeeper motif that integrates upstream signaling pathways to epigenetic regulation and growth control.

The retinoblastoma protein binds E2F residues required for activation in vivo and TBP binding in vitro.

It is shown that the E2F activation domain is the target for RB-induced repression, and that the TATA box binding protein TBP can bind to the E 2Factivation domain in vitro in a manner indistinguishable from that of RB.

Rb Interacts with Histone Deacetylase to Repress Transcription

In Vivo Structure of the Cell Cycle-regulated Humancdc25C Promoter*

Micrococcus nuclease and methidiumpropyl-EDTA footprinting strongly suggest that the proximal promoter encompassing the cell cycle-dependent element/cell cycle genes homology region and the upstream NF-Y sites is organized in a positioned nucleosome throughout the cell Cycle.