TY - JOUR
T1 - Anti-silencing factor epe1 associates with SAGA to regulate transcription within heterochromatin
AU - Bao, Kehan
AU - Shan, Chun Min
AU - Moresco, James
AU - Yates, John
AU - Jia, Songtao
N1 - Funding Information:
We thank Jiyong Wang for technical assistance, Alok Nimgaon-kar for assistance with validating results of the SGA screen, Fred Winston for yeast strains, Michael Keogh for the HA antibody, James Manley for Pol II antibody, and Arjun Srivatsa and Tasneem Ebrahim for critical reading of the manuscript. This work was supported by National Institutes of Health grants R01-GM085145 and R35-GM126910 to S.J., the National Center for Research Resources (P41-RR011823), and the National Institute of General Medical Sciences (P41-GM103533).
Publisher Copyright:
© 2019 Bao, et al.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Heterochromatin is a highly condensed form of chromatin that silences gene transcription. Although high levels of transcriptional activities disrupt heterochromatin, transcription of repetitive DNA elements and subsequent processing of the transcripts by the RNAi machinery are required for heterochromatin assembly. In fission yeast, a JmjC domain protein, Epe1, promotes transcription of DNA repeats to facilitate heterochromatin formation, but overexpression of Epe1 leads to heterochromatin defects. However, the molecular function of Epe1 is not well understood. By screening the fission yeast deletion library, we found that heterochromatin defects associated with Epe1 overexpression are alleviated by mutations of the SAGA histone acetyltransferase complex. Overexpressed Epe1 associates with SAGA and recruits SAGA to heterochromatin regions, which leads to increased histone acetylation, transcription of repeats, and the disruption of heterochromatin. At its normal expression levels, Epe1 also associates with SAGA, albeit weakly. Such interaction regulates histone acetylation levels at heterochromatin and promotes transcription of repeats for heterochromatin assembly. Our results also suggest that increases of certain chromatin protein levels, which frequently occur in cancer cells, might strengthen relatively weak interactions to affect the epigenetic landscape.
AB - Heterochromatin is a highly condensed form of chromatin that silences gene transcription. Although high levels of transcriptional activities disrupt heterochromatin, transcription of repetitive DNA elements and subsequent processing of the transcripts by the RNAi machinery are required for heterochromatin assembly. In fission yeast, a JmjC domain protein, Epe1, promotes transcription of DNA repeats to facilitate heterochromatin formation, but overexpression of Epe1 leads to heterochromatin defects. However, the molecular function of Epe1 is not well understood. By screening the fission yeast deletion library, we found that heterochromatin defects associated with Epe1 overexpression are alleviated by mutations of the SAGA histone acetyltransferase complex. Overexpressed Epe1 associates with SAGA and recruits SAGA to heterochromatin regions, which leads to increased histone acetylation, transcription of repeats, and the disruption of heterochromatin. At its normal expression levels, Epe1 also associates with SAGA, albeit weakly. Such interaction regulates histone acetylation levels at heterochromatin and promotes transcription of repeats for heterochromatin assembly. Our results also suggest that increases of certain chromatin protein levels, which frequently occur in cancer cells, might strengthen relatively weak interactions to affect the epigenetic landscape.
KW - Epe1
KW - Heterochromatin
KW - Histone
KW - Methylation
KW - SAGA
KW - Transcription
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U2 - 10.1101/gad.318030.118
DO - 10.1101/gad.318030.118
M3 - Article
C2 - 30573453
AN - SCOPUS:85059495049
SN - 0890-9369
VL - 33
SP - 116
EP - 126
JO - Genes and Development
JF - Genes and Development
IS - 1-2
ER -