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A new companion of elongating RNA Polymerase II: TINTIN, an independent sub-module of NuA4/TIP60 for nucleosome transactions.

Cheng X, Côté J - Transcription (2015)

Bottom Line: Multiple factors are involved in the elongation stage of transcription regulation to ensure the passing of RNA polymerases while preserving appropriate nucleosome structure thereafter.The recently reported trimeric sub-module of NuA4 histone acetyltransferase complex involved in this process provides more insight into the sophisticated modulation of transcription elongation.

View Article: PubMed Central - PubMed

Affiliation: a St-Patrick Research Group in Basic Oncology ; Laval University Cancer Research Center and CHU de Quebec Research Center-Oncology Axis ; Hôtel-Dieu de Québec (CHU de Québec); Quebec City , QC Canada.

ABSTRACT
Multiple factors are involved in the elongation stage of transcription regulation to ensure the passing of RNA polymerases while preserving appropriate nucleosome structure thereafter. The recently reported trimeric sub-module of NuA4 histone acetyltransferase complex involved in this process provides more insight into the sophisticated modulation of transcription elongation.

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Related in: MedlinePlus

Model for the involvement of TINTIN in nucleosome transactions during transcription elongation. TINTIN represents a trimeric module which exists both within and outside of the NuA4/TIP60 histone acetyltransferase (HAT) complex. It interacts with phosphorylated CTD domain of RNAP II and Set2-mediated H3K36me3-containing nucleosomes during transcription elongation. In front of elongating RNAP II, TINTIN-containing NuA4 acetylates nucleosomes to assist nucleosome disruption. Behind the polymerase, independent TINTIN assists recycling/refolding of nucleosomes in coordination with FACT and Spt6 histone chaperones. This, together with the deacetylation of reassembled nucleosomes by Rpd3S histone deacetylase (HDAC) complex, contributes to the suppression of new histone incorporation (by Asf1/Rtt109).
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f0001: Model for the involvement of TINTIN in nucleosome transactions during transcription elongation. TINTIN represents a trimeric module which exists both within and outside of the NuA4/TIP60 histone acetyltransferase (HAT) complex. It interacts with phosphorylated CTD domain of RNAP II and Set2-mediated H3K36me3-containing nucleosomes during transcription elongation. In front of elongating RNAP II, TINTIN-containing NuA4 acetylates nucleosomes to assist nucleosome disruption. Behind the polymerase, independent TINTIN assists recycling/refolding of nucleosomes in coordination with FACT and Spt6 histone chaperones. This, together with the deacetylation of reassembled nucleosomes by Rpd3S histone deacetylase (HDAC) complex, contributes to the suppression of new histone incorporation (by Asf1/Rtt109).

Mentions: The detailed chromatin environment required for proper transcription elongation regulation remains to be elucidated. Eaf3 not only resides in Rpd3S, but is also a subunit of another complex with opposing activity, the NuA4 histone acetyltransferase complex. While Rpd3S is associated with repressed chromatin structure of coding regions as mentioned above, NuA4 is generally linked to transcriptional activation by its acetylation activity in “opening” promoter nucleosomes.14-17 The question is, as both Rpd3S and NuA4 complexes contain Eaf3, why Eaf3 only directs Rpd3S to H3K36me3 over gene bodies, but not NuA4? Subsequent studies have shown that it is the combination of Eaf3 chromo domain and PHD domain in Rpd3S specific subunit Rco1 that endows the specificity,18 along interaction with phosphorylated RNAP II.19,20 NuA4 itself had been detected on coding regions of some genes and histone methylation has been implicated in this binding.21,22 Nevertheless, this is evidently not the end of the story. Adding to the complexity, recently we provided evidence for the presence of Eaf3 in another small complex consisting of Eaf5/Eaf7/Eaf3.23 Biochemical data show that Eaf5/7/3 are stable subunits of NuA4 yet can exist as an independent trimeric subcomplex. Compared to NuA4, this trimer exhibits more enrichment over coding regions relative to promoters in genomic mapping, suggesting the involvement in transcription elongation. Additional experiments show that the trimer actually travels with elongating RNAP II over the gene bodies by utilizing a dual interaction surface with both H3K36me3 and phosphorylated RNAP II (Ser2). In contrast to the effect of Rpd3S, this association to coding regions seems to destabilize nucleosomes, as mutants suppress cryptic transcription detected in Set2 deletion strains. Intriguingly, by interacting with histone chaperons, it also helps recycle/refold nucleosomes after the passage of RNAP II, preventing the incorporation of new histones. These results gave rise to a model in which the trimer stimulates disruption of nucleosomes in front of the polymerase through its association with NuA4 acetyltransferase activity. In parallel it also stabilizes chromatin in the wake of RNAP II by assisting chaperone-mediated recycling/reassembly of the disrupted nucleosomes, a function independent of NuA4. Due to its biochemical characteristics and molecular functions, this newly characterized sub-module is named as the TINTIN complex, for Trimer Independent of NuA4 involved in Transcription Interactions with Nucleosomes (Fig. 1).Figure 1.


A new companion of elongating RNA Polymerase II: TINTIN, an independent sub-module of NuA4/TIP60 for nucleosome transactions.

Cheng X, Côté J - Transcription (2015)

Model for the involvement of TINTIN in nucleosome transactions during transcription elongation. TINTIN represents a trimeric module which exists both within and outside of the NuA4/TIP60 histone acetyltransferase (HAT) complex. It interacts with phosphorylated CTD domain of RNAP II and Set2-mediated H3K36me3-containing nucleosomes during transcription elongation. In front of elongating RNAP II, TINTIN-containing NuA4 acetylates nucleosomes to assist nucleosome disruption. Behind the polymerase, independent TINTIN assists recycling/refolding of nucleosomes in coordination with FACT and Spt6 histone chaperones. This, together with the deacetylation of reassembled nucleosomes by Rpd3S histone deacetylase (HDAC) complex, contributes to the suppression of new histone incorporation (by Asf1/Rtt109).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581353&req=5

f0001: Model for the involvement of TINTIN in nucleosome transactions during transcription elongation. TINTIN represents a trimeric module which exists both within and outside of the NuA4/TIP60 histone acetyltransferase (HAT) complex. It interacts with phosphorylated CTD domain of RNAP II and Set2-mediated H3K36me3-containing nucleosomes during transcription elongation. In front of elongating RNAP II, TINTIN-containing NuA4 acetylates nucleosomes to assist nucleosome disruption. Behind the polymerase, independent TINTIN assists recycling/refolding of nucleosomes in coordination with FACT and Spt6 histone chaperones. This, together with the deacetylation of reassembled nucleosomes by Rpd3S histone deacetylase (HDAC) complex, contributes to the suppression of new histone incorporation (by Asf1/Rtt109).
Mentions: The detailed chromatin environment required for proper transcription elongation regulation remains to be elucidated. Eaf3 not only resides in Rpd3S, but is also a subunit of another complex with opposing activity, the NuA4 histone acetyltransferase complex. While Rpd3S is associated with repressed chromatin structure of coding regions as mentioned above, NuA4 is generally linked to transcriptional activation by its acetylation activity in “opening” promoter nucleosomes.14-17 The question is, as both Rpd3S and NuA4 complexes contain Eaf3, why Eaf3 only directs Rpd3S to H3K36me3 over gene bodies, but not NuA4? Subsequent studies have shown that it is the combination of Eaf3 chromo domain and PHD domain in Rpd3S specific subunit Rco1 that endows the specificity,18 along interaction with phosphorylated RNAP II.19,20 NuA4 itself had been detected on coding regions of some genes and histone methylation has been implicated in this binding.21,22 Nevertheless, this is evidently not the end of the story. Adding to the complexity, recently we provided evidence for the presence of Eaf3 in another small complex consisting of Eaf5/Eaf7/Eaf3.23 Biochemical data show that Eaf5/7/3 are stable subunits of NuA4 yet can exist as an independent trimeric subcomplex. Compared to NuA4, this trimer exhibits more enrichment over coding regions relative to promoters in genomic mapping, suggesting the involvement in transcription elongation. Additional experiments show that the trimer actually travels with elongating RNAP II over the gene bodies by utilizing a dual interaction surface with both H3K36me3 and phosphorylated RNAP II (Ser2). In contrast to the effect of Rpd3S, this association to coding regions seems to destabilize nucleosomes, as mutants suppress cryptic transcription detected in Set2 deletion strains. Intriguingly, by interacting with histone chaperons, it also helps recycle/refold nucleosomes after the passage of RNAP II, preventing the incorporation of new histones. These results gave rise to a model in which the trimer stimulates disruption of nucleosomes in front of the polymerase through its association with NuA4 acetyltransferase activity. In parallel it also stabilizes chromatin in the wake of RNAP II by assisting chaperone-mediated recycling/reassembly of the disrupted nucleosomes, a function independent of NuA4. Due to its biochemical characteristics and molecular functions, this newly characterized sub-module is named as the TINTIN complex, for Trimer Independent of NuA4 involved in Transcription Interactions with Nucleosomes (Fig. 1).Figure 1.

Bottom Line: Multiple factors are involved in the elongation stage of transcription regulation to ensure the passing of RNA polymerases while preserving appropriate nucleosome structure thereafter.The recently reported trimeric sub-module of NuA4 histone acetyltransferase complex involved in this process provides more insight into the sophisticated modulation of transcription elongation.

View Article: PubMed Central - PubMed

Affiliation: a St-Patrick Research Group in Basic Oncology ; Laval University Cancer Research Center and CHU de Quebec Research Center-Oncology Axis ; Hôtel-Dieu de Québec (CHU de Québec); Quebec City , QC Canada.

ABSTRACT
Multiple factors are involved in the elongation stage of transcription regulation to ensure the passing of RNA polymerases while preserving appropriate nucleosome structure thereafter. The recently reported trimeric sub-module of NuA4 histone acetyltransferase complex involved in this process provides more insight into the sophisticated modulation of transcription elongation.

Show MeSH
Related in: MedlinePlus