SETDB1 modulates PRC2 activity at developmental genes independently of H3K9 trimethylation in mouse ES cells

Qi, Fei; Yang, Xiaoqin; Jiang, Hua; Qian, Wang; Yu, Yanyan; Yu, Yiling; Yi, Wei; Zhou, Shaolian; Chen, Taiping; Atadja, Peter; Liu, Xiaole Shirley; Li, En; Zhang, Yong; Shou, Jianyong

doi:10.1101/gr.177576.114

Cited by 34 publications

(31 citation statements)

References 47 publications

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“…For comparison to other ChIP-seq data sets, we analyzed published datasets: ATRX (GSM551138)(Law et al, 2010), CTCF (GSM1540992)(Kung et al, 2015), Ezh2 (GSM905437)(Pinter et al, 2012), PolIIS5 (GSM905442)(Pinter et al, 2012), H3K4me3 (GSM905439)(Pinter et al, 2012), H3K9me3 (GSM1531184)(Fei et al, 2015), H3K27me3 (GSM905438)(Pinter et al, 2012), SMC1 (GSM560341)(Kagey et al, 2010) and H3K36me3 (GSM905441)(Pinter et al, 2012). Fastq files were aligned to the mm10 genome using Bowtie2 (-k 1 –very-sensitive –no-disordant) (Langmead and Salzberg, 2012).…”

Section: Methods Detailsmentioning

confidence: 99%

“…Multiple studies have implicated TERRA as regulator of telomerase and telomere length (Sandell et al, 1994; Redon et al, 2010; Maicher et al, 2012; Pfeiffer and Lingner, 2012; Fei et al, 2015). TERRA has also been proposed to regulate recombination between telomeric ends (Balk et al, 2013; de Silanes et al, 2014; Yu et al, 2014) and serve as a scaffold for recruitment of chromatin factors such as HP1, histone methyltransferases, and shelterins to telomeric heterochromatin (Deng et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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TERRA RNA Antagonizes ATRX and Protects Telomeres

Chu

Cifuentes-Rojas

Kesner

et al. 2017

Cell

215

290

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Summary Through an integration of genomic and proteomic approaches to advance understanding of long noncoding RNAs, we investigate the function of the telomeric transcript, TERRA. By identifying thousands of TERRA target sites in the mouse genome, we demonstrate that TERRA can bind both in cis to telomeres and in trans to genic targets. We then define a large network of interacting proteins, including epigenetic factors, telomeric proteins, and the RNA helicase, ATRX. TERRA and ATRX share hundreds of target genes and are functionally antagonistic at these loci: Whereas TERRA activates, ATRX represses gene expression. At telomeres, TERRA competes with telomeric DNA for ATRX binding, suppresses ATRX localization, and ensures telomeric stability. Depleting TERRA increases telomerase activity and induces telomeric pathologies, including formation of telomere-induced DNA damage foci and loss or duplication of telomeric sequences. We conclude that TERRA functions as epigenomic modulator in trans and as essential regulator of telomeres in cis.

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Section: Methods Detailsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TERRA RNA Antagonizes ATRX and Protects Telomeres

Chu

Cifuentes-Rojas

Kesner

et al. 2017

Cell

215

290

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“…Furthermore, Fei et al . have reported that the interaction between ESET and PRC2 maintains the pluripotency of ES cells. Thus, the down‐regulation of differentiation‐related genes by ESET may be crucial for maintaining the multipotency of mouse neural crest cells and for the formation of mouse NCSCs.…”

Section: Discussionmentioning

confidence: 99%

CHD7, Oct3/4, Sox2, and Nanog control FoxD3 expression during mouse neural crest‐derived stem cell formation

Fujita

Ogawa

2016

The FEBS Journal

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Neural crest-derived stem cells (NCSCs) are tissue-specific stem cells derived from multipotent neural crest cells. NCSCs are present in some adult tissues such as dorsal root ganglia, sciatic nerve, and bone marrow. However, little is known about the formation mechanisms of these cells. We have shown that BMP2/Wnt3a signaling and a chromatin remodeler, CHD7, in mice help to maintain the multipotency of neural crest cells and lead to the formation of NCSCs. In the present study, we analyzed a regulatory gene cascade in the formation of mouse NCSCs. The inhibition of FoxD3 expression significantly suppressed the expression of Sox10, which is an indispensable transcription factor for mouse NCSC formation, in the presence of BMP2/Wnt3a. CHD7, Oct3/4, Sox2, and Nanog occupied multiple conserved regions of mouse FoxD3, mE1, mE2, and mE3, in a BMP2/Wnt3a-dependent manner. Furthermore, siRNA of CHD7, Oct3/4, Sox2, and Nanog significantly suppressed FoxD3 expression. The inhibition of histone H3K4 mono- or trimethylation also repressed FoxD3 expression. The present data suggest that CHD7, Oct3/4, Sox2, and Nanog directly induce FoxD3 expression when stimulated by BMP2/Wnt3a signaling, that FoxD3 promotes Sox10 expression, and that histone H3K4 methylation plays important roles in this process of mouse NCSC formation.

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“…Further adding to this lack of clarity on the role of JARID2 in modulation of PRC2 activity, in in vitro studies JARID2 appears to inhibit (Peng et al, 2009;Shen et al, 2009) as well as activate (Li et al, 2010) the methyltransferase activity of EZH2. A recent study has also shown that, in mouse ES cells, JARID2 can modulate PRC2 activity through its interaction with another histone methylase, setDB1 (Fei et al, 2015). A recent study has also shown that, in mouse ES cells, JARID2 can modulate PRC2 activity through its interaction with another histone methylase, setDB1 (Fei et al, 2015).…”

Section: Introductionmentioning

confidence: 97%

“…It has been suggested that JARID2's N-terminal domain interacts with RNAs as well as nucleosomes (Son et al, 2013;Kaneko et al, 2014b) and its post-translational modifications determine its effect on PRC2 activity (Sanulli et al, 2015). A recent study has also shown that, in mouse ES cells, JARID2 can modulate PRC2 activity through its interaction with another histone methylase, setDB1 (Fei et al, 2015). JARID2-setDB1 interaction has also been identified in lineage-committed cells including lymphocytes (Macian et al, 2002;Pereira et al, 2014) and cardiomyocytes where JARID2 is shown to modulate other histone modifications such as H3K9me3.…”

Section: Introductionmentioning

confidence: 99%

A novel form of JARID2 is required for differentiation in lineage‐committed cells

et al. 2018

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Polycomb repressive complex‐2 (PRC2) is a group of proteins that play an important role during development and in cell differentiation. PRC2 is a histone‐modifying complex that catalyses methylation of lysine 27 of histone H3 (H3K27me3) at differentiation genes leading to their transcriptional repression. JARID2 is a co‐factor of PRC2 and is important for targeting PRC2 to chromatin. Here, we show that, unlike in embryonic stem cells, in lineage‐committed human cells, including human epidermal keratinocytes, JARID2 predominantly exists as a novel low molecular weight form, which lacks the N‐terminal PRC2‐interacting domain (ΔN‐JARID2). We show that ΔN‐JARID2 is a cleaved product of full‐length JARID2 spanning the C‐terminal conserved jumonji domains. JARID2 knockout in keratinocytes results in up‐regulation of cell cycle genes and repression of many epidermal differentiation genes. Surprisingly, repression of epidermal differentiation genes in JARID2‐null keratinocytes can be rescued by expression of ΔN‐JARID2 suggesting that, in contrast to PRC2, ΔN‐JARID2 promotes activation of differentiation genes. We propose that a switch from expression of full‐length JARID2 to ΔN‐JARID2 is important for the up‐regulation differentiation genes.

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SETDB1 modulates PRC2 activity at developmental genes independently of H3K9 trimethylation in mouse ES cells

Cited by 34 publications

References 47 publications

TERRA RNA Antagonizes ATRX and Protects Telomeres

TERRA RNA Antagonizes ATRX and Protects Telomeres

CHD7, Oct3/4, Sox2, and Nanog control FoxD3 expression during mouse neural crest‐derived stem cell formation

A novel form of JARID2 is required for differentiation in lineage‐committed cells

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