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Hsp90 affecting chromatin remodeling might explain transgenerational epigenetic inheritance in Drosophila.

Ruden DM, Lu X - Curr. Genomics (2008)

Bottom Line: Among their other activities, PcG complexes cause histone 3 lysine 27 tri-methylation associated with repressed chromatin, whereas Trithorax group (TrxG) complexes induce histone 3 lysine 4 tri-methylation associated with actively transcribed chromatin.Consistent with this model, Hsp90 has recently been shown to be a chaperone for Tah1p (TPR-containing protein associated with Hsp90) and Pih1p (protein interacting with Hsp90), which connect to the chromatin remodelling factor Rvb1p (RuvB-like protein 1)/Rvb2p in yeast [1].Since PcG and TrxG complexes are involved in the post-translational modifications of histones, and since such modifications have been shown to be required to maintain imprinted marks, this unified mechanism might also help to explain transgenerational epigenetic inheritance in humans.

View Article: PubMed Central - PubMed

Affiliation: Wayne State University, Institute for Environmental Health Sciences, 2727 2 Ave, Room 4000, Detroit, MI 48201, USA.

ABSTRACT
Transgenerational epigenetic inheritance, while poorly understood, is of great interest because it might help explain the increase in the incidence of diseases with an environmental contribution in humans, such as cancer, diabetes, and heart disease. Here, we review five Drosophila examples of transgenerational epigenetic inheritance and propose a unified mechanism that involves Polycomb Response Element/Trithorax Response Element (PRE/TRE) occupancy by either Polycomb Group (PcG) protein complexes or Trithorax group (TrxG) complexes. Among their other activities, PcG complexes cause histone 3 lysine 27 tri-methylation associated with repressed chromatin, whereas Trithorax group (TrxG) complexes induce histone 3 lysine 4 tri-methylation associated with actively transcribed chromatin. In this model, Hsp90 is an environmentally sensitive chromatin remodeling regulator that causes a switch in the chromatin from a permissive state to a non-permissive state for transcription. Consistent with this model, Hsp90 has recently been shown to be a chaperone for Tah1p (TPR-containing protein associated with Hsp90) and Pih1p (protein interacting with Hsp90), which connect to the chromatin remodelling factor Rvb1p (RuvB-like protein 1)/Rvb2p in yeast [1]. Also, Hsp90 is required for optimal activity of the histone H3 lysine-4 methyltransferase SMYD3 in mammals [2, 3]. Since PcG and TrxG complexes are involved in the post-translational modifications of histones, and since such modifications have been shown to be required to maintain imprinted marks, this unified mechanism might also help to explain transgenerational epigenetic inheritance in humans.

No MeSH data available.


Related in: MedlinePlus

TrxG proteins (stars) form a complex on a PRE/TRE. Trithorax is a protein in the TrxG complex that tri-methylates Histone 3 lysine 4, which is an epigenetic mark that is associated with actively transcribed genes. In this model, Hsp90 is a chaperone for the chromatin-remodeling protein Rvb1p and/or TrxG proteins Trithorax and Ash1.Stress functionally inactivates Hsp90, thereby causing a replacement of the TrxG proteins at the PRE/TRE by PcG proteins (hexagons). Enhancer of zeste, E(z), is a protein in the PcG complex that tri-methylates Histone 3 lysine 27, which is an epigenetic mark that is associated with chromatin that is not permissive for transcription.
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Figure 1: TrxG proteins (stars) form a complex on a PRE/TRE. Trithorax is a protein in the TrxG complex that tri-methylates Histone 3 lysine 4, which is an epigenetic mark that is associated with actively transcribed genes. In this model, Hsp90 is a chaperone for the chromatin-remodeling protein Rvb1p and/or TrxG proteins Trithorax and Ash1.Stress functionally inactivates Hsp90, thereby causing a replacement of the TrxG proteins at the PRE/TRE by PcG proteins (hexagons). Enhancer of zeste, E(z), is a protein in the PcG complex that tri-methylates Histone 3 lysine 27, which is an epigenetic mark that is associated with chromatin that is not permissive for transcription.

Mentions: Currently, there are over a dozen members of the Pc Group (PcG) with similar phenotypes [35]. The PcG proteins and complexes are conserved from Drosophila to humans and are involved in the long-term maintenance of the repressed state of target genes during development (for review, see [32]). The precise mechanism by which PcG proteins maintain the repressed state of target genes is not known, but it is likely to involve the establishment of “repressive chromatin marks” on the histones, such as Histone 3 Lysine 27 tri-methylation (H3K27me3) by the PcG protein E(z) (Fig. 1B) [36, 37].


Hsp90 affecting chromatin remodeling might explain transgenerational epigenetic inheritance in Drosophila.

Ruden DM, Lu X - Curr. Genomics (2008)

TrxG proteins (stars) form a complex on a PRE/TRE. Trithorax is a protein in the TrxG complex that tri-methylates Histone 3 lysine 4, which is an epigenetic mark that is associated with actively transcribed genes. In this model, Hsp90 is a chaperone for the chromatin-remodeling protein Rvb1p and/or TrxG proteins Trithorax and Ash1.Stress functionally inactivates Hsp90, thereby causing a replacement of the TrxG proteins at the PRE/TRE by PcG proteins (hexagons). Enhancer of zeste, E(z), is a protein in the PcG complex that tri-methylates Histone 3 lysine 27, which is an epigenetic mark that is associated with chromatin that is not permissive for transcription.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2691676&req=5

Figure 1: TrxG proteins (stars) form a complex on a PRE/TRE. Trithorax is a protein in the TrxG complex that tri-methylates Histone 3 lysine 4, which is an epigenetic mark that is associated with actively transcribed genes. In this model, Hsp90 is a chaperone for the chromatin-remodeling protein Rvb1p and/or TrxG proteins Trithorax and Ash1.Stress functionally inactivates Hsp90, thereby causing a replacement of the TrxG proteins at the PRE/TRE by PcG proteins (hexagons). Enhancer of zeste, E(z), is a protein in the PcG complex that tri-methylates Histone 3 lysine 27, which is an epigenetic mark that is associated with chromatin that is not permissive for transcription.
Mentions: Currently, there are over a dozen members of the Pc Group (PcG) with similar phenotypes [35]. The PcG proteins and complexes are conserved from Drosophila to humans and are involved in the long-term maintenance of the repressed state of target genes during development (for review, see [32]). The precise mechanism by which PcG proteins maintain the repressed state of target genes is not known, but it is likely to involve the establishment of “repressive chromatin marks” on the histones, such as Histone 3 Lysine 27 tri-methylation (H3K27me3) by the PcG protein E(z) (Fig. 1B) [36, 37].

Bottom Line: Among their other activities, PcG complexes cause histone 3 lysine 27 tri-methylation associated with repressed chromatin, whereas Trithorax group (TrxG) complexes induce histone 3 lysine 4 tri-methylation associated with actively transcribed chromatin.Consistent with this model, Hsp90 has recently been shown to be a chaperone for Tah1p (TPR-containing protein associated with Hsp90) and Pih1p (protein interacting with Hsp90), which connect to the chromatin remodelling factor Rvb1p (RuvB-like protein 1)/Rvb2p in yeast [1].Since PcG and TrxG complexes are involved in the post-translational modifications of histones, and since such modifications have been shown to be required to maintain imprinted marks, this unified mechanism might also help to explain transgenerational epigenetic inheritance in humans.

View Article: PubMed Central - PubMed

Affiliation: Wayne State University, Institute for Environmental Health Sciences, 2727 2 Ave, Room 4000, Detroit, MI 48201, USA.

ABSTRACT
Transgenerational epigenetic inheritance, while poorly understood, is of great interest because it might help explain the increase in the incidence of diseases with an environmental contribution in humans, such as cancer, diabetes, and heart disease. Here, we review five Drosophila examples of transgenerational epigenetic inheritance and propose a unified mechanism that involves Polycomb Response Element/Trithorax Response Element (PRE/TRE) occupancy by either Polycomb Group (PcG) protein complexes or Trithorax group (TrxG) complexes. Among their other activities, PcG complexes cause histone 3 lysine 27 tri-methylation associated with repressed chromatin, whereas Trithorax group (TrxG) complexes induce histone 3 lysine 4 tri-methylation associated with actively transcribed chromatin. In this model, Hsp90 is an environmentally sensitive chromatin remodeling regulator that causes a switch in the chromatin from a permissive state to a non-permissive state for transcription. Consistent with this model, Hsp90 has recently been shown to be a chaperone for Tah1p (TPR-containing protein associated with Hsp90) and Pih1p (protein interacting with Hsp90), which connect to the chromatin remodelling factor Rvb1p (RuvB-like protein 1)/Rvb2p in yeast [1]. Also, Hsp90 is required for optimal activity of the histone H3 lysine-4 methyltransferase SMYD3 in mammals [2, 3]. Since PcG and TrxG complexes are involved in the post-translational modifications of histones, and since such modifications have been shown to be required to maintain imprinted marks, this unified mechanism might also help to explain transgenerational epigenetic inheritance in humans.

No MeSH data available.


Related in: MedlinePlus