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H2A.Z-mediated localization of genes at the nuclear periphery confers epigenetic memory of previous transcriptional state.

Brickner DG, Cajigas I, Fondufe-Mittendorf Y, Ahmed S, Lee PC, Widom J, Brickner JH - PLoS Biol. (2007)

Bottom Line: This form of transcriptional memory is chromatin based; the histone variant H2A.Z is incorporated into nucleosomes within the recently repressed INO1 promoter and is specifically required for rapid reactivation of both INO1 and GAL1.Furthermore, H2A.Z is required to retain INO1 at the nuclear periphery after repression.Therefore, H2A.Z-mediated localization of recently repressed genes at the nuclear periphery represents an epigenetic state that confers memory of transcriptional activation and promotes reactivation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois, United States of America.

ABSTRACT
Many genes are recruited to the nuclear periphery upon transcriptional activation. The mechanism and functional significance of this recruitment is unclear. We find that recruitment of the yeast INO1 and GAL1 genes to the nuclear periphery is rapid and independent of transcription. Surprisingly, these genes remain at the periphery for generations after they are repressed. Localization at the nuclear periphery serves as a form of memory of recent transcriptional activation, promoting reactivation. Previously expressed GAL1 at the nuclear periphery is activated much more rapidly than long-term repressed GAL1 in the nucleoplasm, even after six generations of repression. Localization of INO1 at the nuclear periphery is necessary and sufficient to promote more rapid activation. This form of transcriptional memory is chromatin based; the histone variant H2A.Z is incorporated into nucleosomes within the recently repressed INO1 promoter and is specifically required for rapid reactivation of both INO1 and GAL1. Furthermore, H2A.Z is required to retain INO1 at the nuclear periphery after repression. Therefore, H2A.Z-mediated localization of recently repressed genes at the nuclear periphery represents an epigenetic state that confers memory of transcriptional activation and promotes reactivation.

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Htz1 Is Required for Transcriptional Memory(A and B) Strains BY4741 and BY4741 htz1Δ from either short-term (3 h) repressing conditions (A) or long-term repressing conditions (B) were shifted into medium without inositol and collected at the indicated time points. The INO1 and ACT1 mRNA levels were quantified by RT Q-PCR.(C and D) Strains BY4741 and BY4741 swr1Δ from either short-term (3 h) repressing conditions (A) or long-term repressing conditions (B) were shifted into medium without inositol and collected at the indicated time points. The INO1 and ACT1 mRNA levels were quantified by RT Q-PCR.(E and F) Strains BY4741 and BY4741 htz1Δ from either short-term (12 h) repressing conditions (E) or long-term repressing conditions (F) were shifted into galactose medium and collected at the indicated time points. The GAL1 and ACT1 mRNA levels were quantified by RT Q-PCR.
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pbio-0050081-g006: Htz1 Is Required for Transcriptional Memory(A and B) Strains BY4741 and BY4741 htz1Δ from either short-term (3 h) repressing conditions (A) or long-term repressing conditions (B) were shifted into medium without inositol and collected at the indicated time points. The INO1 and ACT1 mRNA levels were quantified by RT Q-PCR.(C and D) Strains BY4741 and BY4741 swr1Δ from either short-term (3 h) repressing conditions (A) or long-term repressing conditions (B) were shifted into medium without inositol and collected at the indicated time points. The INO1 and ACT1 mRNA levels were quantified by RT Q-PCR.(E and F) Strains BY4741 and BY4741 htz1Δ from either short-term (12 h) repressing conditions (E) or long-term repressing conditions (F) were shifted into galactose medium and collected at the indicated time points. The GAL1 and ACT1 mRNA levels were quantified by RT Q-PCR.

Mentions: Yeast H2A.Z is encoded by the non-essential HTZ1 gene [39]. To test if H2A.Z is important for transcriptional memory, we compared the rates of reactivation of recently repressed INO1 and GAL1 in wild-type and htz1Δ mutant cells (Figure 6). Loss of H2A.Z led to a strong delay in the rate of reactivation of both short-term repressed INO1 and short-term repressed GAL1 (Figure 6A and 6E). Surprisingly, loss of H2A.Z had no effect on the rate of activation of long-term repressed INO1 or GAL1 (Figure 6B and 6F). These results suggest that H2A.Z plays an important and specific role in the reactivation of these genes. H2A.Z is exchanged for H2A within intact nucleosomes by the SWR1 ATPase complex [40–42]. To test if SWR1 plays a role in the H2A.Z-dependent reactivation of INO1, we next tested the effect of loss of SWR1 on INO1 activation and reactivation. We find that swr1Δ mutant strains were also defective for reactivation of recently repressed INO1 (Figure 6C), and had little effect on the activation of long-term repressed INO1 (Figure 6D).


H2A.Z-mediated localization of genes at the nuclear periphery confers epigenetic memory of previous transcriptional state.

Brickner DG, Cajigas I, Fondufe-Mittendorf Y, Ahmed S, Lee PC, Widom J, Brickner JH - PLoS Biol. (2007)

Htz1 Is Required for Transcriptional Memory(A and B) Strains BY4741 and BY4741 htz1Δ from either short-term (3 h) repressing conditions (A) or long-term repressing conditions (B) were shifted into medium without inositol and collected at the indicated time points. The INO1 and ACT1 mRNA levels were quantified by RT Q-PCR.(C and D) Strains BY4741 and BY4741 swr1Δ from either short-term (3 h) repressing conditions (A) or long-term repressing conditions (B) were shifted into medium without inositol and collected at the indicated time points. The INO1 and ACT1 mRNA levels were quantified by RT Q-PCR.(E and F) Strains BY4741 and BY4741 htz1Δ from either short-term (12 h) repressing conditions (E) or long-term repressing conditions (F) were shifted into galactose medium and collected at the indicated time points. The GAL1 and ACT1 mRNA levels were quantified by RT Q-PCR.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1828143&req=5

pbio-0050081-g006: Htz1 Is Required for Transcriptional Memory(A and B) Strains BY4741 and BY4741 htz1Δ from either short-term (3 h) repressing conditions (A) or long-term repressing conditions (B) were shifted into medium without inositol and collected at the indicated time points. The INO1 and ACT1 mRNA levels were quantified by RT Q-PCR.(C and D) Strains BY4741 and BY4741 swr1Δ from either short-term (3 h) repressing conditions (A) or long-term repressing conditions (B) were shifted into medium without inositol and collected at the indicated time points. The INO1 and ACT1 mRNA levels were quantified by RT Q-PCR.(E and F) Strains BY4741 and BY4741 htz1Δ from either short-term (12 h) repressing conditions (E) or long-term repressing conditions (F) were shifted into galactose medium and collected at the indicated time points. The GAL1 and ACT1 mRNA levels were quantified by RT Q-PCR.
Mentions: Yeast H2A.Z is encoded by the non-essential HTZ1 gene [39]. To test if H2A.Z is important for transcriptional memory, we compared the rates of reactivation of recently repressed INO1 and GAL1 in wild-type and htz1Δ mutant cells (Figure 6). Loss of H2A.Z led to a strong delay in the rate of reactivation of both short-term repressed INO1 and short-term repressed GAL1 (Figure 6A and 6E). Surprisingly, loss of H2A.Z had no effect on the rate of activation of long-term repressed INO1 or GAL1 (Figure 6B and 6F). These results suggest that H2A.Z plays an important and specific role in the reactivation of these genes. H2A.Z is exchanged for H2A within intact nucleosomes by the SWR1 ATPase complex [40–42]. To test if SWR1 plays a role in the H2A.Z-dependent reactivation of INO1, we next tested the effect of loss of SWR1 on INO1 activation and reactivation. We find that swr1Δ mutant strains were also defective for reactivation of recently repressed INO1 (Figure 6C), and had little effect on the activation of long-term repressed INO1 (Figure 6D).

Bottom Line: This form of transcriptional memory is chromatin based; the histone variant H2A.Z is incorporated into nucleosomes within the recently repressed INO1 promoter and is specifically required for rapid reactivation of both INO1 and GAL1.Furthermore, H2A.Z is required to retain INO1 at the nuclear periphery after repression.Therefore, H2A.Z-mediated localization of recently repressed genes at the nuclear periphery represents an epigenetic state that confers memory of transcriptional activation and promotes reactivation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois, United States of America.

ABSTRACT
Many genes are recruited to the nuclear periphery upon transcriptional activation. The mechanism and functional significance of this recruitment is unclear. We find that recruitment of the yeast INO1 and GAL1 genes to the nuclear periphery is rapid and independent of transcription. Surprisingly, these genes remain at the periphery for generations after they are repressed. Localization at the nuclear periphery serves as a form of memory of recent transcriptional activation, promoting reactivation. Previously expressed GAL1 at the nuclear periphery is activated much more rapidly than long-term repressed GAL1 in the nucleoplasm, even after six generations of repression. Localization of INO1 at the nuclear periphery is necessary and sufficient to promote more rapid activation. This form of transcriptional memory is chromatin based; the histone variant H2A.Z is incorporated into nucleosomes within the recently repressed INO1 promoter and is specifically required for rapid reactivation of both INO1 and GAL1. Furthermore, H2A.Z is required to retain INO1 at the nuclear periphery after repression. Therefore, H2A.Z-mediated localization of recently repressed genes at the nuclear periphery represents an epigenetic state that confers memory of transcriptional activation and promotes reactivation.

Show MeSH
Related in: MedlinePlus