Similar Datasets
Project description:Polycomb-group proteins play critical roles in gene silencing through the deposition of histone H3 lysine 27 trimethylation (H3K27me3) and chromatin compaction. This process is essential for embryonic stem cells (ESCs) pluripotency, differentiation, and development. Polycomb repressive complex 2 (PRC2) can both read and write H3K27me3, enabling processive spread of H3K27me3 on linear genome and epigenetic memory. Long-range Polycomb-associated DNA contacts have also been described, but their regulation and role in gene silencing remains unclear. Here, we develop H3K27me3 HiChIP and apply optical reconstruction of chromatin architecture to reveal long-range Polycomb-associated DNA loops that span tens to hundreds of megabases and across multiple topological associated domains in mouse ESCs and human induced pluripotent stem cells. H3K27me3 loop anchors are enriched for Polycomb nucleation points and coincide with key developmental genes, such as Hmx1, Wnt6 and Hoxa. Genetic deletion of H3K27me3 loop anchors causes spatially proximal partner chromosomal loci to break apart, and alters H3K27me3 deposition, both locally and megabases away on the same chromosome. A selective EZH2 mutant deficient in RNA binding but intact H3K27me3 enzymatic activity leads to global alteration in H3K27me3 loops, decreased spatial proximity, and failure to spread Polycomb from PRC2 nucleation points to partner loci at developmental genes. Together, these results suggest PRC2 acts as a “genomic wormhole”, using RNA binding to enhance long range chromosome folding and H3K27me3 spreading. Developmental gene loci have novel roles in Polycomb spreading, emerging as key architectural elements of the epigenome.
2022-05-13 | GSE150906 | GEO
Project description:Polycomb-group proteins play critical roles in gene silencing through the deposition of histone H3 lysine 27 trimethylation (H3K27me3) and chromatin compaction. This process is essential for embryonic stem cells (ESCs) pluripotency, differentiation, and development. Polycomb repressive complex 2 (PRC2) can both read and write H3K27me3, enabling processive spread of H3K27me3 on linear genome and epigenetic memory. Long-range Polycomb-associated DNA contacts have also been described, but their regulation and role in gene silencing remains unclear. Here, we develop H3K27me3 HiChIP and apply optical reconstruction of chromatin architecture to reveal long-range Polycomb-associated DNA loops that span tens to hundreds of megabases and across multiple topological associated domains in mouse ESCs and human induced pluripotent stem cells. H3K27me3 loop anchors are enriched for Polycomb nucleation points and coincide with key developmental genes, such as Hmx1, Wnt6 and Hoxa. Genetic deletion of H3K27me3 loop anchors causes spatially proximal partner chromosomal loci to break apart, and alters H3K27me3 deposition, both locally and megabases away on the same chromosome. A selective EZH2 mutant deficient in RNA binding but intact H3K27me3 enzymatic activity leads to global alteration in H3K27me3 loops, decreased spatial proximity, and failure to spread Polycomb from PRC2 nucleation points to partner loci at developmental genes. Together, these results suggest PRC2 acts as a “genomic wormhole”, using RNA binding to enhance long range chromosome folding and H3K27me3 spreading. Developmental gene loci have novel roles in Polycomb spreading, emerging as key architectural elements of the epigenome.
2022-05-13 | GSE150905 | GEO
Project description:Polycomb-group proteins play critical roles in gene silencing through the deposition of histone H3 lysine 27 trimethylation (H3K27me3) and chromatin compaction. This process is essential for embryonic stem cells (ESCs) pluripotency, differentiation, and development. Polycomb repressive complex 2 (PRC2) can both read and write H3K27me3, enabling processive spread of H3K27me3 on linear genome and epigenetic memory. Long-range Polycomb-associated DNA contacts have also been described, but their regulation and role in gene silencing remains unclear. Here, we develop H3K27me3 HiChIP and apply optical reconstruction of chromatin architecture to reveal long-range Polycomb-associated DNA loops that span tens to hundreds of megabases and across multiple topological associated domains in mouse ESCs and human induced pluripotent stem cells. H3K27me3 loop anchors are enriched for Polycomb nucleation points and coincide with key developmental genes, such as Hmx1, Wnt6 and Hoxa. Genetic deletion of H3K27me3 loop anchors causes spatially proximal partner chromosomal loci to break apart, and alters H3K27me3 deposition, both locally and megabases away on the same chromosome. A selective EZH2 mutant deficient in RNA binding but intact H3K27me3 enzymatic activity leads to global alteration in H3K27me3 loops, decreased spatial proximity, and failure to spread Polycomb from PRC2 nucleation points to partner loci at developmental genes. Together, these results suggest PRC2 acts as a “genomic wormhole”, using RNA binding to enhance long range chromosome folding and H3K27me3 spreading. Developmental gene loci have novel roles in Polycomb spreading, emerging as key architectural elements of the epigenome.
2022-05-13 | GSE150904 | GEO
Project description:Polycomb-group proteins play critical roles in gene silencing through the deposition of histone H3 lysine 27 trimethylation (H3K27me3) and chromatin compaction. This process is essential for embryonic stem cells (ESCs) pluripotency, differentiation, and development. Polycomb repressive complex 2 (PRC2) can both read and write H3K27me3, enabling processive spread of H3K27me3 on linear genome and epigenetic memory. Long-range Polycomb-associated DNA contacts have also been described, but their regulation and role in gene silencing remains unclear. Here, we develop H3K27me3 HiChIP and apply optical reconstruction of chromatin architecture to reveal long-range Polycomb-associated DNA loops that span tens to hundreds of megabases and across multiple topological associated domains in mouse ESCs and human induced pluripotent stem cells. H3K27me3 loop anchors are enriched for Polycomb nucleation points and coincide with key developmental genes, such as Hmx1, Wnt6 and Hoxa. Genetic deletion of H3K27me3 loop anchors causes spatially proximal partner chromosomal loci to break apart, and alters H3K27me3 deposition, both locally and megabases away on the same chromosome. A selective EZH2 mutant deficient in RNA binding but intact H3K27me3 enzymatic activity leads to global alteration in H3K27me3 loops, decreased spatial proximity, and failure to spread Polycomb from PRC2 nucleation points to partner loci at developmental genes. Together, these results suggest PRC2 acts as a “genomic wormhole”, using RNA binding to enhance long range chromosome folding and H3K27me3 spreading. Developmental gene loci have novel roles in Polycomb spreading, emerging as key architectural elements of the epigenome.
2022-05-13 | GSE196526 | GEO
Project description:Polycomb-mediated genome architecture enables long-range spreading of H3K27 methylation
| PRJNA634024 | ENA
Project description:Polycomb-mediated genome architecture enables long-range spreading of H3K27 methylation [HiChIP]
| PRJNA634029 | ENA
Project description:Polycomb-mediated genome architecture enables long-range spreading of H3K27 methylation [RNA-Seq]
| PRJNA805252 | ENA
Project description:Polycomb-mediated genome architecture enables long-range spreading of H3K27 methylation [4C-seq]
| PRJNA634027 | ENA
Project description:Polycomb-mediated genome architecture enables long-range spreading of H3K27 methylation [Cut&Tag]
| PRJNA634028 | ENA
Project description:H3K27 methylation mediated by the histone methyltransferase complex PRC2 is critical for transcriptional regulation, Polycomb silencing, Drosophila segmentation, mammalian X chromosome inactivation, and cancer. PRC2-mediated H3K27 methylation can spread along the chromatin and propagate the repressive chromatin environment; thus, chromatin components that antagonize the activity of PRC2 are important for restraining Polycomb silencing. Here we report that in HeLa cells, H3 histones unmethylated at Lys-36 are mostly methylated at Lys-27, with the exception of newly synthesized H3. In addition, K27me3 rarely co-exists with K36me2 or K36me3 on the same histone H3 polypeptide. Moreover, PRC2 activity is greatly inhibited on nucleosomal substrates with preinstalled H3K36 methylation. These findings collectively identify H3K36 methylation as a chromatin component that restricts the PRC2-mediated spread of H3K27 methylation. Finally, we provide evidence that the controversial histone lysine methyltransferase Ash1, a known Trithorax group protein that antagonizes Polycomb silencing in vivo, is an H3K36-specific dimethylase, not an H3K4 methylase, further supporting the role of H3K36 methylation in antagonizing PRC2-mediated H3K27 methylation.
| S-EPMC3048685 | biostudies-literature