Similar Datasets
Project description:The genetic information encoded in DNA is framed by additional layers of information, referred to as the epigenome. Epigenetic marks such as DNA methylation, histone modifications and histone variants are concentrated on specific genomic sites as means to instruct, but also sometimes as a consequence of, gene expression. How this information is maintained, notably in the face of transcription, is not understood. Here we show that the histone chaperones FACT and Spt6 are required for maintaining proper localization of several histone modifications including H3K4me1,2,3, H3K36me3, H3K79me3, H3K14ac, H3K18ac and H2Bub in Saccharomyces cerevisiae. In the absence of functional FACT or Spt6, transcription generates massive nucleosome loss which is partially compensated by increased histone assembly by histone chaperones such as Asf1 and HIR. Because re-incorporation of histones by these histone chaperones in not coupled to transcription, the modified histones are randomly incorporated, leading to scrambling of the epigenetic information. Hence, our work highlights the importance of local nucleosome recycling by FACT and Spt6 during transcription in the maintenance of a proper epigenetic landscape.
2019-07-30 | GSE113025 | GEO
Project description:The genetic information encoded in DNA is framed by additional layers of information, referred to as the epigenome. Epigenetic marks such as DNA methylation, histone modifications and histone variants are concentrated on specific genomic sites as means to instruct, but also sometimes as a consequence of, gene expression. How this information is maintained, notably in the face of transcription, is not understood. Here we show that the histone chaperones FACT and Spt6 are required for maintaining proper localization of several histone modifications including H3K4me1,2,3, H3K36me3, H3K79me3, H3K14ac, H3K18ac and H2Bub in Saccharomyces cerevisiae. In the absence of functional FACT or Spt6, transcription generates massive nucleosome loss which is partially compensated by increased histone assembly by histone chaperones such as Asf1 and HIR. Because re-incorporation of histones by these histone chaperones in not coupled to transcription, the modified histones are randomly incorporated, leading to scrambling of the epigenetic information. Hence, our work highlights the importance of local nucleosome recycling by FACT and Spt6 during transcription in the maintenance of a proper epigenetic landscape.
2019-07-30 | GSE113213 | GEO
Project description:Histone Recycling by FACT and Spt6 during Transcription Prevents the Scrambling of Histone Modifications
| PRJNA450619 | ENA
Project description:Histone Recycling by FACT and Spt6 during Transcription Prevents the Scrambling of Histone Modifications [tiling]
| PRJNA449917 | ENA
Project description:Histone Recycling by FACT and Spt6 during Transcription Prevents the Scrambling of Histone Modifications [ChIP-seq]
| PRJNA450434 | ENA
Project description:The tail of histone H3 is an ideal medium for storing epigenetic information because displacement of histone H3 is heavily restricted during transcription. To maintain the locus-specific modifications of histone H3, histone molecules should be retained locally at the original position through multiple rounds of transcription. Here, we found that fission yeast Spt6, a highly conserved RNA polymerase II-interacting histone H3-H4 chaperone, is essential for the maintenance of Lys-4 and Lys-9 methylation of histone H3 in euchromatin and heterochromatin, respectively. In euchromatin, loss of Lys-4 methylated histone H3 and deposition of newly synthesized Lys-56 acetylated histone H3 induced by Spt6 inactivation were coupled with transcription. While in heterochromatin, Spt6 prevents histone turnover and cryptic transcription in parallel with Clr3 histone deacetylase. We propose that Spt6 retains posttranslationally modified histone H3 during transcription to maintain epigenome integrity.
| S-EPMC3711048 | biostudies-literature
Project description:H2A.Z is a highly conserved histone variant involved in several key nuclear processes. It is incorporated into promoters by SWR-C-related chromatin remodeling complexes, but whether it is also actively excluded from non-promoter regions is not clear. Here we provide genomic and biochemical evidence that the RNA polymerase II (RNA Pol II) elongation-associated histone chaperones FACT and Spt6 both contribute to restricting H2A.Z from intragenic regions. In the absence of FACT or Spt6, the lack of efficient nucleosome reassembly coupled to pervasive incorporation of H2A.Z by mislocalized SWR-C alters chromatin composition and contributes to cryptic initiation. Therefore, chaperone-mediated H2A.Z confinement is crucial for restricting the chromatin signature of gene promoters that otherwise may license or promote cryptic transcription.
| S-EPMC4475440 | biostudies-literature
Project description:Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression. To gain a comprehensive understanding of the roles of Spt6, we performed genome-wide analyses of transcription, chromatin structure, and histone modifications in a Schizosaccharomyces pombe spt6 mutant. Our results demonstrate dramatic changes to transcription and chromatin structure in the mutant, including elevated antisense transcripts at >70% of all genes and general loss of the +1 nucleosome. Furthermore, Spt6 is required for marks associated with active transcription, including trimethylation of histone H3 on lysine 4, previously observed in humans but not Saccharomyces cerevisiae, and lysine 36. Taken together, our results indicate that Spt6 is critical for the accuracy of transcription and the integrity of chromatin, likely via its direct interactions with RNA polymerase II and histones.
| S-EPMC3889546 | biostudies-literature
Project description:Histone H3 of nucleosomes positioned on active genes is trimethylated at Lys36 (H3K36me3) by the SETD2 (also termed KMT3A/SET2 or HYPB) methyltransferase. Previous studies in yeast indicated that H3K36me3 prevents spurious intragenic transcription initiation through recruitment of a histone deacetylase complex, a mechanism that is not conserved in mammals. Here, we report that downregulation of SETD2 in human cells leads to intragenic transcription initiation in at least 11% of active genes. Reduction of SETD2 prevents normal loading of the FACT (FAcilitates Chromatin Transcription) complex subunits SPT16 and SSRP1, and decreases nucleosome occupancy in active genes. Moreover, co-immunoprecipitation experiments suggest that SPT16 is recruited to active chromatin templates, which contain H3K36me3-modified nucleosomes. Our results further show that within minutes after transcriptional activation, there is a SETD2-dependent reduction in gene body occupancy of histone H2B, but not of histone H3, suggesting that SETD2 coordinates FACT-mediated exchange of histone H2B during transcription-coupled nucleosome displacement. After inhibition of transcription, we observe a SETD2-dependent recruitment of FACT and increased histone H2B occupancy. These data suggest that SETD2 activity modulates FACT recruitment and nucleosome dynamics, thereby repressing cryptic transcription initiation.
| S-EPMC3597667 | biostudies-literature
Project description:FACT (facilitates chromatin transcription) is a histone chaperone that promotes chromatin recovery during transcription, with additional roles in cell differentiation. Although several models of the action of FACT during transcription have been proposed, they remain to be experimentally evaluated. Here we show that human FACT (hFACT) facilitates transcription through chromatin and promotes nucleosome recovery in vitro. FACT action depends on the presence of histone H2A/H2B dimers in the nucleosome. Kinetic analysis suggests that hFACT decreases the lifetime of nonproductive RNA polymerase II (Pol II)-nucleosome complexes and facilitates the formation of productive complexes containing nucleosomal DNA partially uncoiled from the octamer. Taken together, our data suggest that hFACT interacts with DNA-binding surfaces of H2A/H2B dimers, facilitating uncoiling of DNA from the histone octamer. Thus, hFACT-H2A/H2B interactions play a key role in overcoming the nucleosomal barrier by Pol II and promoting nucleosome survival during transcription.
| S-EPMC3651417 | biostudies-literature