Ash1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract polycomb silencing.
Molecular mechanisms for the establishment of transcriptional memory are poorly understood. 5,6-dichloro-1-D-ribofuranosyl-benzimidazole (DRB) is a P-TEFb kinase inhibitor that artificially induces the poised RNA polymerase II (RNAPII), thereby manifesting intermediate steps for the establishment of...
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2013
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oai:doaj.org-article:3ee68ac1ba8943e2b8344a2f9d326ec52021-11-18T06:21:36ZAsh1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract polycomb silencing.1553-73901553-740410.1371/journal.pgen.1003897https://doaj.org/article/3ee68ac1ba8943e2b8344a2f9d326ec52013-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24244179/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Molecular mechanisms for the establishment of transcriptional memory are poorly understood. 5,6-dichloro-1-D-ribofuranosyl-benzimidazole (DRB) is a P-TEFb kinase inhibitor that artificially induces the poised RNA polymerase II (RNAPII), thereby manifesting intermediate steps for the establishment of transcriptional activation. Here, using genetics and DRB, we show that mammalian Absent, small, or homeotic discs 1-like (Ash1l), a member of the trithorax group proteins, methylates Lys36 of histone H3 to promote the establishment of Hox gene expression by counteracting Polycomb silencing. Importantly, we found that Ash1l-dependent Lys36 di-, tri-methylation of histone H3 in a coding region and exclusion of Polycomb group proteins occur independently of transcriptional elongation in embryonic stem (ES) cells, although both were previously thought to be consequences of transcription. Genome-wide analyses of histone H3 Lys36 methylation under DRB treatment have suggested that binding of the retinoic acid receptor (RAR) to a certain genomic region promotes trimethylation in the RAR-associated gene independent of its ongoing transcription. Moreover, DRB treatment unveils a parallel response between Lys36 methylation of histone H3 and occupancy of either Tip60 or Mof in a region-dependent manner. We also found that Brg1 is another key player involved in the response. Our results uncover a novel regulatory cascade orchestrated by Ash1l with RAR and provide insights into mechanisms underlying the establishment of the transcriptional activation that counteracts Polycomb silencing.Hitomi MiyazakiKen HigashimotoYukari YadaTakaho A EndoJafar SharifToshiharu KomoriMasashi MatsudaYoko KosekiManabu NakayamaHidenobu SoejimaHiroshi HandaHaruhiko KosekiSusumu HiroseKenichi NishiokaPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 9, Iss 11, p e1003897 (2013) |
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DOAJ |
| collection |
DOAJ |
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| topic |
Genetics QH426-470 |
| spellingShingle |
Genetics QH426-470 Hitomi Miyazaki Ken Higashimoto Yukari Yada Takaho A Endo Jafar Sharif Toshiharu Komori Masashi Matsuda Yoko Koseki Manabu Nakayama Hidenobu Soejima Hiroshi Handa Haruhiko Koseki Susumu Hirose Kenichi Nishioka Ash1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract polycomb silencing. |
| description |
Molecular mechanisms for the establishment of transcriptional memory are poorly understood. 5,6-dichloro-1-D-ribofuranosyl-benzimidazole (DRB) is a P-TEFb kinase inhibitor that artificially induces the poised RNA polymerase II (RNAPII), thereby manifesting intermediate steps for the establishment of transcriptional activation. Here, using genetics and DRB, we show that mammalian Absent, small, or homeotic discs 1-like (Ash1l), a member of the trithorax group proteins, methylates Lys36 of histone H3 to promote the establishment of Hox gene expression by counteracting Polycomb silencing. Importantly, we found that Ash1l-dependent Lys36 di-, tri-methylation of histone H3 in a coding region and exclusion of Polycomb group proteins occur independently of transcriptional elongation in embryonic stem (ES) cells, although both were previously thought to be consequences of transcription. Genome-wide analyses of histone H3 Lys36 methylation under DRB treatment have suggested that binding of the retinoic acid receptor (RAR) to a certain genomic region promotes trimethylation in the RAR-associated gene independent of its ongoing transcription. Moreover, DRB treatment unveils a parallel response between Lys36 methylation of histone H3 and occupancy of either Tip60 or Mof in a region-dependent manner. We also found that Brg1 is another key player involved in the response. Our results uncover a novel regulatory cascade orchestrated by Ash1l with RAR and provide insights into mechanisms underlying the establishment of the transcriptional activation that counteracts Polycomb silencing. |
| format |
article |
| author |
Hitomi Miyazaki Ken Higashimoto Yukari Yada Takaho A Endo Jafar Sharif Toshiharu Komori Masashi Matsuda Yoko Koseki Manabu Nakayama Hidenobu Soejima Hiroshi Handa Haruhiko Koseki Susumu Hirose Kenichi Nishioka |
| author_facet |
Hitomi Miyazaki Ken Higashimoto Yukari Yada Takaho A Endo Jafar Sharif Toshiharu Komori Masashi Matsuda Yoko Koseki Manabu Nakayama Hidenobu Soejima Hiroshi Handa Haruhiko Koseki Susumu Hirose Kenichi Nishioka |
| author_sort |
Hitomi Miyazaki |
| title |
Ash1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract polycomb silencing. |
| title_short |
Ash1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract polycomb silencing. |
| title_full |
Ash1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract polycomb silencing. |
| title_fullStr |
Ash1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract polycomb silencing. |
| title_full_unstemmed |
Ash1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract polycomb silencing. |
| title_sort |
ash1l methylates lys36 of histone h3 independently of transcriptional elongation to counteract polycomb silencing. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/3ee68ac1ba8943e2b8344a2f9d326ec5 |
| work_keys_str_mv |
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| _version_ |
1718424472487198720 |