Set1/COMPASS and Mediator are repurposed to promote epigenetic transcriptional memory DOI Creative Commons

Agustina D’Urso,

Yoh-hei Takahashi,

Bin Xiong

и другие.

eLife, Год журнала: 2016, Номер 5

Опубликована: Июнь 23, 2016

In yeast and humans, previous experiences can lead to epigenetic transcriptional memory: repressed genes that exhibit mitotically heritable changes in chromatin structure promoter recruitment of poised RNA polymerase II preinitiation complex (RNAPII PIC), which enhances future reactivation. Here, we show INO1 memory is initiated by binding the Sfl1 transcription factor cis-acting Memory Recruitment Sequence, targeting nuclear periphery. requires a remodeled form Set1/COMPASS methyltransferase lacking Spp1, dimethylates histone H3 lysine 4 (H3K4me2). H3K4me2 recruits SET3C complex, plays an essential role maintaining this mark. Finally, while active associated with Cdk8- Mediator, during memory, Cdk8+ Mediator RNAPII PIC Kin28 CTD kinase. Aspects mechanism are generalizable conserved human cells. Thus, COMPASS repurposed promote poising highly mechanism.

Язык: Английский

EGFR Mutation Promotes Glioblastoma through Epigenome and Transcription Factor Network Remodeling DOI Creative Commons
Feng Liu, Gary C. Hon, Genaro R. Villa

и другие.

Molecular Cell, Год журнала: 2015, Номер 60(2), С. 307 - 318

Опубликована: Окт. 1, 2015

Язык: Английский

Процитировано

178
Interrogating the Function of Metazoan Histones using Engineered Gene Clusters DOI Creative Commons
Daniel J. McKay, Stephen Klusza,

Taylor J.R. Penke

и другие.

Developmental Cell, Год журнала: 2015, Номер 32(3), С. 373 - 386

Опубликована: Фев. 1, 2015

Язык: Английский

Процитировано

166
Multiple modes of PRC2 inhibition elicit global chromatin alterations in H3K27M pediatric glioma DOI Creative Commons
James M. Stafford, Chul‐Hwan Lee, Philipp Voigt

и другие.

Science Advances, Год журнала: 2018, Номер 4(10)

Опубликована: Окт. 5, 2018

A methionine substitution at lysine-27 on histone H3 variants (H3K27M) characterizes ~80% of diffuse intrinsic pontine gliomas (DIPG) and inhibits polycomb repressive complex 2 (PRC2) in a dominant-negative fashion. Yet, the mechanisms for this inhibition abnormal epigenomic landscape have not been resolved. Using quantitative proteomics, we discovered that robust PRC2 requires levels H3K27M greatly exceeding those PRC2, seen DIPG. While interaction with H3K27M, found chromatin is transient, largely being released from H3K27M. Unexpectedly, persisted even after dissociated H3K27M-containing chromatin, suggesting lasting impact PRC2. Furthermore, allosterically activated particularly sensitive to leading failure spread H3K27me recruitment sites consequently abrogating PRC2's ability establish H3K27me2-3 domains. In turn, antagonists such as H3K36me2 are elevated, more global, downstream effect epigenome. Together, these findings reveal conditions required H3K27M-mediated reconcile seemingly paradoxical effects activity.

Язык: Английский

Процитировано

161
Resetting the epigenetic balance of Polycomb and COMPASS function at enhancers for cancer therapy DOI
Lu Wang, Zibo Zhao, Patrick A. Ozark

и другие.

Nature Medicine, Год журнала: 2018, Номер 24(6), С. 758 - 769

Опубликована: Май 18, 2018

Язык: Английский

Процитировано

144
Set1/COMPASS and Mediator are repurposed to promote epigenetic transcriptional memory DOI Creative Commons

Agustina D’Urso,

Yoh-hei Takahashi,

Bin Xiong

и другие.

eLife, Год журнала: 2016, Номер 5

Опубликована: Июнь 23, 2016

In yeast and humans, previous experiences can lead to epigenetic transcriptional memory: repressed genes that exhibit mitotically heritable changes in chromatin structure promoter recruitment of poised RNA polymerase II preinitiation complex (RNAPII PIC), which enhances future reactivation. Here, we show INO1 memory is initiated by binding the Sfl1 transcription factor cis-acting Memory Recruitment Sequence, targeting nuclear periphery. requires a remodeled form Set1/COMPASS methyltransferase lacking Spp1, dimethylates histone H3 lysine 4 (H3K4me2). H3K4me2 recruits SET3C complex, plays an essential role maintaining this mark. Finally, while active associated with Cdk8- Mediator, during memory, Cdk8+ Mediator RNAPII PIC Kin28 CTD kinase. Aspects mechanism are generalizable conserved human cells. Thus, COMPASS repurposed promote poising highly mechanism.

Язык: Английский

Процитировано

138