scholarly journals Ash1l Methylates Lys36 of Histone H3 Independently of Transcriptional Elongation to Counteract Polycomb Silencing

PLoS Genetics ◽  
2013 ◽  
Vol 9 (11) ◽  
pp. e1003897 ◽  
Author(s):  
Hitomi Miyazaki ◽  
Ken Higashimoto ◽  
Yukari Yada ◽  
Takaho A. Endo ◽  
Jafar Sharif ◽  
...  
Keyword(s):  
Histone H3 ◽  
Transcriptional Elongation

scholarly journals Promoter-specific changes in initiation, elongation and homeostasis of histone H3 acetylation during CBP/p300 inhibition

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Emily Hsu ◽  
Nathan R Zemke ◽  
Arnold J Berk
Keyword(s):  
Rna Polymerase Ii ◽  
Control Point ◽  
Histone H3 ◽  
Airway Epithelial Cells ◽  
Proximal Region ◽  
Transferase Activity ◽  
Transcriptional Elongation ◽  
Elongation Complex ◽  
Histone H3 Acetylation ◽  
H3 Acetylation

Regulation of RNA Polymerase II (Pol2) elongation in the promoter proximal region is an important and ubiquitous control point for gene expression in metazoans. We report that transcription of the adenovirus 5 E4 region is regulated during the release of paused Pol2 into productive elongation by recruitment of the super elongation complex (SEC), dependent on promoter H3K18/27 acetylation by CBP/p300. We also establish that this is a general transcriptional regulatory mechanism that applies to ~6% of expressed protein-coding genes in primary human airway epithelial cells. We observed that a homeostatic mechanism maintains promoter, but not enhancer H3K18/27ac in response to extensive inhibition of CBP/p300 acetyl transferase activity by the highly specific small molecule inhibitor A-485. Further, our results suggest a function for BRD4 association at enhancers in regulating paused Pol2 release at nearby promoters. Taken together, our results uncover processes regulating transcriptional elongation by promoter region histone H3 acetylation and homeostatic maintenance of promoter, but not enhancer, H3K18/27ac in response to inhibition of CBP/p300 acetyl transferase activity.

scholarly journals A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification

Blood ◽  
2007 ◽  
Vol 110 (13) ◽  
pp. 4445-4454 ◽  
Author(s):  
Dorothee Mueller ◽  
Christian Bach ◽  
Deniz Zeisig ◽  
Maria-Paz Garcia-Cuellar ◽  
Sara Monroe ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Chromatin Modification ◽  
Histone H3 ◽  
Elongation Factor ◽  
Polycomb Group ◽  
Fusion Partner ◽  
Transcriptional Elongation ◽  
Associated Proteins ◽  
Group Members

Chimeric proteins joining the histone methyltransferase MLL with various fusion partners trigger distinctive lymphoid and myeloid leukemias. Here, we immunopurified proteins associated with ENL, a protein commonly fused to MLL. Identification of these ENL-associated proteins (EAPs) by mass spectrometry revealed enzymes with a known role in transcriptional elongation (RNA polymerase II C-terminal domain kinase [RNAPolII CTD] positive transcription elongation factor b [pTEFb]), and in chromatin modification (histone-H3 methyltransferase DOT1L) as well as other frequent MLL partners (AF4, AF5q31, and LAF4), and polycomb group members (RING1, CBX8, and BCoR). The composition of EAP was further verified by coimmunoprecipitation, 2-hybrid analysis, pull-down, and colocalization experiments. Purified EAP showed a histone H3 lysine 79–specific methylase activity, displayed a robust RNAPolII CTD kinase function, and counteracted the effect of the pTEFb inhibitor 5,6-dichloro-benzimidazole-riboside. In vivo, an ENL knock-down diminished genome-wide as well as gene-specific H3K79 dimethylation, reduced global run-on elongation, and inhibited transient transcriptional reporter activity. According to structure-function data, DOT1L recruitment was important for transformation by the MLL-ENL fusion derivative. These results suggest a function of ENL in histone modification and transcriptional elongation.

scholarly journals Elongator: An Ancestral Complex Driving Transcription and Migration through Protein Acetylation

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Catherine Creppe ◽  
Marcus Buschbeck
Keyword(s):  
Intracellular Trafficking ◽  
Histone H3 ◽  
Transferase Activity ◽  
Transcriptional Elongation ◽  
Protein Acetylation ◽  
Cellular Functions ◽  
Elongator Complex ◽  
And Migration ◽  
Inducible Genes ◽  
Distal Gene

Elongator is an evolutionary highly conserved complex. At least two of its cellular functions rely on the intrinsic lysine acetyl-transferase activity of the Elongator complex. Its two known substrates—Histone H3 and α-Tubulin—reflect the different roles of Elongator in the cytosol and the nucleus. A picture seems to emerge in which nuclear Elongator could regulate the transcriptional elongation of a subset of stress-inducible genes through acetylation of Histone H3 in the promoter-distal gene body. In the cytosol, Elongator-mediated acetylation of α-Tubulin contributes to intracellular trafficking and cell migration. Defects in both functions of Elongator have been implicated in neurodegenerative disorders.

scholarly journals Promoter-specific changes in initiation, elongation and homeostasis of histone H3 acetylation during CBP/p300 Inhibition

2020 ◽  
Author(s):  
E Hsu ◽  
NR Zemke ◽  
AJ Berk
Keyword(s):  
Rna Polymerase Ii ◽  
Control Point ◽  
Histone H3 ◽  
Airway Epithelial Cells ◽  
Proximal Region ◽  
Transferase Activity ◽  
Transcriptional Elongation ◽  
Elongation Complex ◽  
Histone H3 Acetylation ◽  
H3 Acetylation

SummaryRegulation of RNA Polymerase II (Pol2) elongation in the promoter proximal region is an important and ubiquitous control point for gene expression in metazoan cells. We report that transcription of the adenovirus 5 E4 region is regulated during the release of paused Pol2 into productive elongation by recruitment of the super elongation complex (SEC), dependent on promoter H3K18/27 acetylation by CBP/p300. We also establish that this is a general transcriptional regulatory mechanism for ∼6% of genes expressed with FPKM>1 in primary human airway epithelial cells. We observed that a homeostatic mechanism maintains promoter, but not enhancer H3K18/27ac in response to extensive inhibition of CBP/p300 acetyl transferase activity by the highly specific small molecule inhibitor A-485. Further, our results suggest a function for BRD4 association at enhancers in regulating paused Pol2 release at nearby promoters. Taken together, our results uncover processes regulating transcriptional elongation by promoter region histone H3 acetylation and homeostatic maintenance of promoter, but not enhancer, H3K18/27ac in response to inhibition of CBP/p300 acetyl transferase activity.

scholarly journals Rhythmic E-Box Binding by CLK-CYC Controls Daily Cycles in per and tim Transcription and Chromatin Modifications

2008 ◽  
Vol 28 (14) ◽  
pp. 4642-4652 ◽  
Author(s):  
Pete Taylor ◽  
Paul E. Hardin
Keyword(s):  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Specific Binding ◽  
Histone H3 ◽  
Time Of Day ◽  
Transcriptional Elongation ◽  
Chromatin Modifications ◽  
Pol Ii ◽  
E Box ◽  
E Boxes

ABSTRACT The Drosophila melanogaster circadian oscillator comprises interlocked per/tim and Clk transcriptional feedback loops. In the per/tim loop, CLK-CYC-dependent transcriptional activation is rhythmically repressed by PER or PER-TIM to control circadian gene expression that peaks around dusk. Here we show that rhythmic transcription of per and tim involves time-of-day-specific binding of CLK-CYC and associated cycles in chromatin modifications. Activation of per and tim transcription occurs in concert with CLK-CYC binding to upstream and/or intronic E-boxes, acetylation of histone H3-K9, and trimethylation of histone H3-K4. These events are associated with RNA polymerase II (Pol II) binding to the tim promoter and transcriptional elongation by Pol II that is constitutively bound to the per promoter. Repression of per and tim transcription is associated with PER-dependent reversal of these events. Rhythms in H3-K9 acetylation and H3-K4 trimethylation are also associated with CLOCK-BMAL1-dependent transcription in mammals, indicating that the mechanism that controls rhythmic transcription is a conserved feature of the circadian clock even though feedback repression is mediated by different proteins.

scholarly journals The Paf1 Complex Is Required for Histone H3 Methylation by COMPASS and Dot1p: Linking Transcriptional Elongation to Histone Methylation

2003 ◽  
Vol 11 (3) ◽  
pp. 721-729 ◽  
Author(s):  
Nevan J. Krogan ◽  
Jim Dover ◽  
Adam Wood ◽  
Jessica Schneider ◽  
Jonathan Heidt ◽  
...  
Keyword(s):  
Histone Methylation ◽  
Histone H3 ◽  
Transcriptional Elongation ◽  
Histone H3 Methylation ◽  
Paf1 Complex

scholarly journals Methylation of Histone H3 by Set2 in Saccharomyces cerevisiae Is Linked to Transcriptional Elongation by RNA Polymerase II

2003 ◽  
Vol 23 (12) ◽  
pp. 4207-4218 ◽  
Author(s):  
Nevan J. Krogan ◽  
Minkyu Kim ◽  
Amy Tong ◽  
Ashkan Golshani ◽  
Gerard Cagney ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Histone H3 ◽  
Elongation Factor ◽  
Transcriptional Elongation ◽  
Histone H2a ◽  
Ww Domain ◽  
Growth Defects ◽  
C Terminus ◽  
Active Transcription

ABSTRACT Set2 methylates Lys36 of histone H3. We show here that yeast Set2 copurifies with RNA polymerase II (RNAPII). Chromatin immunoprecipitation analyses demonstrated that Set2 and histone H3 Lys36 methylation are associated with the coding regions of several genes that were tested and correlate with active transcription. Both depend, as well, on the Paf1 elongation factor complex. The C terminus of Set2, which contains a WW domain, is also required for effective Lys36 methylation. Deletion of CTK1, encoding an RNAPII CTD kinase, prevents Lys36 methylation and Set2 recruitment, suggesting that methylation may be triggered by contact of the WW domain or C terminus of Set2 with Ser2-phosphorylated CTD. A set2 deletion results in slight sensitivity to 6-azauracil and much less β-galactosidase produced by a reporter plasmid, resulting from a defect in transcription. In synthetic genetic array (SGA) analysis, synthetic growth defects were obtained when a set2 deletion was combined with deletions of all five components of the Paf1 complex, the chromodomain elongation factor Chd1, the putative elongation factor Soh1, the Bre1 or Lge1 components of the histone H2B ubiquitination complex, or the histone H2A variant Htz1. SET2 also interacts genetically with components of the Set1 and Set3 complexes, suggesting that Set1, Set2, and Set3 similarly affect transcription by RNAPII.

scholarly journals Pdx-1 Links Histone H3-Lys-4 Methylation to RNA Polymerase II Elongation during Activation of Insulin Transcription

2005 ◽  
Vol 280 (43) ◽  
pp. 36244-36253 ◽  
Author(s):  
Joshua Francis ◽  
Swarup K. Chakrabarti ◽  
James C. Garmey ◽  
Raghavendra G. Mirmira
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Chromatin Structure ◽  
Small Interfering Rna ◽  
Histone H3 ◽  
Insulin Gene ◽  
Transcriptional Elongation ◽  
Pol Ii ◽  
Insulin Promoter ◽  
Interfering Rna

Expression of the insulin gene is nearly exclusive to the β cells of the pancreatic islets. Although the sequence-specific transcription factors that regulate insulin expression have been well studied, the interrelationship between these factors, chromatin structure, and transcriptional elongation by RNA polymerase II (pol II) has remained undefined. In this regard, recent studies have begun to establish a role for the methylation of histone H3 in the initiation or elongation of transcription by pol II. To determine a role for the transcriptional activator Pdx-1 in the maintenance of chromatin structure and pol II recruitment at the insulin gene, we performed small interfering RNA-mediated knockdown of Pdx-1 in βTC3 cells and subsequently studied histone modifications and pol II recruitment by chromatin immunoprecipitation. We demonstrated here that the 50% fall in insulin transcription following knockdown of Pdx-1 is accompanied by a 60% fall in dimethylated histone H3-Lys-4 at the insulin promoter. H3-Lys-4 methylation at the insulin promoter may be mediated, at least partially, by the methyltransferase Set9. Immunohistochemical analysis revealed that Set9 is expressed in an islet-enriched pattern in the pancreas, similar to the pattern of Pdx-1 expression. The recruitment of Set9 to the insulin gene appears to be a consequence of its direct interaction with Pdx-1, and small interfering RNA-mediated knockdown of Set9 attenuates insulin transcription. Pdx-1 knockdown was also associated with an overall shift in the recruitment of pol II isoforms to the insulin gene, from an elongation isoform (Ser(P)-2) to an initiation isoform (Ser(P)-5). Our findings therefore suggest a model whereby Pdx-1 plays a novel role in linking H3-Lys-4 dimethylation and pol II elongation to insulin transcription.

scholarly journals JMJD3 acts in tandem with KLF4 to facilitate reprogramming to pluripotency

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yinghua Huang ◽  
Hui Zhang ◽  
Lulu Wang ◽  
Chuanqing Tang ◽  
Xiaogan Qin ◽  
...  
Keyword(s):  
Histone H3 ◽  
The Other ◽  
Cell Reprogramming ◽  
Transcriptional Elongation ◽  
Early Passage ◽  
Independent Manner ◽  
Somatic Cell Reprogramming ◽  
Chromatin Interactions ◽  
Yamanaka Factors ◽  
Pluripotency Genes

Abstract The interplay between the Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) and transcriptional/epigenetic co-regulators in somatic cell reprogramming is incompletely understood. Here, we demonstrate that the histone H3 lysine 27 trimethylation (H3K27me3) demethylase JMJD3 plays conflicting roles in mouse reprogramming. On one side, JMJD3 induces the pro-senescence factor Ink4a and degrades the pluripotency regulator PHF20 in a reprogramming factor-independent manner. On the other side, JMJD3 is specifically recruited by KLF4 to reduce H3K27me3 at both enhancers and promoters of epithelial and pluripotency genes. JMJD3 also promotes enhancer-promoter looping through the cohesin loading factor NIPBL and ultimately transcriptional elongation. This competition of forces can be shifted towards improved reprogramming by using early passage fibroblasts or boosting JMJD3’s catalytic activity with vitamin C. Our work, thus, establishes a multifaceted role for JMJD3, placing it as a key partner of KLF4 and a scaffold that assists chromatin interactions and activates gene transcription.

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