/pdf/heterochromatin-revisited-nat-rev-genet-1s49kjmsfl.pdf

Heterochromatin revisited. Nat Rev Genet

Tri-methylation of histone H3 lysine 9 is important for recruiting heterochromatin protein 1 (HP1) to discrete regions of the genome, thereby regulating gene expression, chromatin packaging and heterochromatin formation Here we show that HP1α, -β, and -γ are released from chromatin during the M phase of the cell cycle, even though tri-methylation levels of histone H3 lysine 9 remain unchanged However, the additional, transient modification of histone H3 by phosphorylation of serine 10 next to the more stable methyl-lysine 9 mark is sufficient to eject HP1 proteins from their binding sites Inhibition or depletion of the mitotic kinase Aurora B, which phosphorylates serine 10 on histone H3, causes retention of HP1 proteins on mitotic chromosomes, suggesting that H3 serine 10 phosphorylation is necessary for the dissociation of HP1 from chromatin in M phase These findings establish a regulatory mechanism of protein–protein interactions, through a combinatorial readout of two adjacent post-translational modifications: a stable methylation and a dynamic phosphorylation mark

Regulation of HP1–chromatin binding by histone H3 methylation and phosphorylation

Histone H3 Lysine 9 Methylation and HP1γ Are Associated with Transcription Elongation through Mammalian Chromatin

From silencing to gene expression: real-time analysis in single cells.

https://www.cell.com/trends/genetics/pdf/S0168-9525(03)00261-0.pdf

Histone lysine methylation: a signature for chromatin function

Heterochromatin protein 1 (HP1) is a conserved chromosomal protein that participates in chromatin packaging and gene silencing. A loss of HP1 leads to lethality in Drosophila and correlates with metastasis in human breast cancer cells. On Drosophila polytene chromosomes HP1 is localized to centric regions, telomeric regions, in a banded pattern along the fourth chromosome, and at many sites scattered throughout the euchromatic arms. Recently, one mechanism of HP1 chromosome association was revealed; the amino-terminal chromo domain of HP1 interacts with methylated lysine nine of histone H3, consistent with the histone code hypothesis. Compelling data support this mechanism of HP1 association at centric regions. Is this the only mechanism by which HP1 associates with chromosomes? Interest is now shifting toward the role of HP1 within euchromatic domains. Accumulating evidence in Drosophila and mammals suggests that HP1 associates with chromosomes through interactions with nonhistone chromosomal proteins at locations other than centric heterochromatin. Does HP1 play a similar role in chromatin packaging and gene regulation at these sites as it does in centric heterochromatin? Does HP1 associate with the same proteins at these sites as it does in centric heterochromatin? A first step toward answering these questions is the identification of sequences associated with HP1 within euchromatic domains. Such sequences are likely to include HP1 “target genes” whose discovery will aid in our understanding of HP1 lethality in Drosophila and metastasis of breast cancer cells.

Does heterochromatin protein 1 always follow code

Heterochromatin protein 1 (HP1) is a conserved non-histone chromosomal protein enriched in heterochromatin. On Drosophila polytene chromosomes, HP1 localizes to centric and telomeric regions, along the fourth chromosome, and to specific sites within euchromatin. HP1 associates with centric regions through an interaction with methylated lysine nine of histone H3, a modification generated by the histone methyltransferase SU(VAR)3-9. This association correlates with a closed chromatin configuration and silencing of euchromatic genes positioned near heterochromatin. To determine whether HP1 is sufficient to nucleate the formation of silent chromatin at non-centric locations, HP1 was tethered to sites within euchromatic regions of Drosophila chromosomes. At 25 out of 26 sites tested, tethered HP1 caused silencing of a nearby reporter gene. The site that did not support silencing was upstream of an active gene, suggesting that the local chromatin environment did not support the formation of silent chromatin. Silencing correlated with the formation of ectopic fibers between the site of tethered HP1 and other chromosomal sites, some containing HP1. The ability of HP1 to bring distant chromosomal sites into proximity with each other suggests a mechanism for chromatin packaging. Silencing was not dependent on SU(VAR)3-9 dosage, suggesting a bypass of the requirement for histone methylation.

/pdf/effects-of-tethering-hp1-to-euchromatic-regions-of-the-1y4cxd93v1.pdf

Effects of tethering HP1 to euchromatic regions of the Drosophila genome.

Heterochromatin protein 1 (HP1), a gene silencing protein, localizes to centric heterochromatin through an interaction with methylated K9 of histone H3, a modification generated by the histone methyl transferase SU(VAR)3-9 On Drosophila polytene chromosomes, HP1 also localizes to 200 sites scattered throughout euchromatin To address the role of HP1 in euchromatic gene regulation, mRNAs from wild-type and Su(var)2-5 mutants lacking HP1 were compared Genes residing within a 550-kb genomic region enriched in HP1 that show altered expression in the Su(var)2-5 mutant were analyzed in detail Three genes within this region, Pros35, CG5676, and cdc2, were found to associate with HP1 by chromatin immunoprecipitation Surprisingly, these genes require HP1 for expression, suggesting a positive role for HP1 in euchromatic gene expression Of these genes, only cdc2 is packaged with methylated K9 H3 Furthermore, none of the genes show altered expression in a Su(var)3-9 mutant Collectively, these data demonstrate multiple mechanisms for HP1 localization within euchromatin and show that some genes associated with HP1 are not affected by alterations in Su(var)3-9 dosage

https://anatomypubs.onlinelibrary.wiley.com/doi/pdf/10.1002/dvdy.20310

Role of Drosophila HP1 in euchromatic gene expression

Lamins are intermediate filaments that line the inner surface of the nuclear envelope, providing structural support and making contacts with chromatin. There are two types of lamins, A- and B-types, which differ in structure and expression. Drosophila possesses both lamin types, encoded by the LamC (A-type) and lamin Dm0 (B-type) genes. LamC is nested within an intron of the essential gene ttv. We demonstrate that null mutations in LamC are lethal, and expression of a wild-type LamC transgene rescues lethality of LamC but not ttv mutants. Mutations in the human A-type lamin gene lead to diseases called laminopathies. To determine if Drosophila might serve as a useful model to study lamin biology and disease mechanisms, we generated transgenic flies expressing mutant LamC proteins modeled after human disease-causing lamins. These transgenic animals display a nuclear lamin aggregation phenotype remarkably similar to that observed when human mutant A-type lamins are expressed in mammalian cells. LamC aggregates also cause disorganization of lamin Dm0, indicating interdependence of both lamin types for proper lamina assembly. Taken together, these data provide the first detailed genetic analysis of the LamC gene and support using Drosophila as a model to study the role of lamins in disease.

https://www.genetics.org/content/genetics/171/1/185.full.pdf

Yuhong Li

Papers

Does heterochromatin protein 1 always follow code

Effects of tethering HP1 to euchromatic regions of the Drosophila genome.

Role of Drosophila HP1 in euchromatic gene expression

Molecular genetic analysis of the nested Drosophila melanogaster lamin C gene.

Conserved properties of HP1Hsα