scholarly journals Dynamics of RNA Polymerase II Pausing and Bivalent Histone H3 Methylation during Neuronal Differentiation in Brain Development

Cell Reports ◽  
2017 ◽  
Vol 20 (6) ◽  
pp. 1307-1318 ◽  
Author(s):  
Jiancheng Liu ◽  
Xiwei Wu ◽  
Heying Zhang ◽  
Gerd P. Pfeifer ◽  
Qiang Lu
2007 ◽  
Vol 28 (3) ◽  
pp. 1041-1046 ◽  
Author(s):  
Edwin R. Smith ◽  
Min Gyu Lee ◽  
Benjamin Winter ◽  
Nathan M. Droz ◽  
Joel C. Eissenberg ◽  
...  

ABSTRACT Histone H3 methylation at Lys27 (H3K27 methylation) is a hallmark of silent chromatin, while H3K4 methylation is associated with active chromatin regions. Here we report that a Drosophila JmjC family member, dUTX, specifically demethylates di- and trimethylated but not monomethylated H3K27. dUTX localization on chromatin correlates with the elongating form of RNA polymerase II (Pol II), and dUTX can associate with Pol II. Furthermore, heat shock induction results in the recruitment of dUTX to the hsp70 gene, like that of several other Pol II elongation factors. Our data indicate that dUTX is intimately associated with actively transcribed genes and may provide a paradigm for how H3K27 demethylation is required for the activation of preinitiated Pol II on transcriptionally poised genes.


2004 ◽  
Vol 24 (7) ◽  
pp. 2932-2943 ◽  
Author(s):  
Hailing Cheng ◽  
Xiaoyuan He ◽  
Claire Moore

ABSTRACT Swd2, an essential WD repeat protein in Saccharomyces cerevisiae, is a component of two very different complexes: the cleavage and polyadenylation factor CPF and the Set1 methylase, which modifies lysine 4 of histone H3 (H3-K4). It was not known if Swd2 is important for the function of either of these entities. We show here that, in extract from cells depleted of Swd2, cleavage and polyadenylation of the mRNA precursor in vitro are completely normal. However, temperature-sensitive mutations or depletion of Swd2 causes termination defects in some genes transcribed by RNA polymerase II. Overexpression of Ref2, a protein previously implicated in snoRNA 3′ end formation and Swd2 recruitment to CPF, can rescue the growth and termination defects, indicating a functional interaction between the two proteins. Some swd2 mutations also significantly decrease global H3-K4 methylation and cause other phenotypes associated with loss of this chromatin modification, such as loss of telomere silencing, hydroxyurea sensitivity, and alterations in repression of INO1 transcription. Even though the two Swd2-containing complexes are both localized to actively transcribed genes, the allele specificities of swd2 defects suggest that the functions of Swd2 in mediating RNA polymerase II termination and H3-K4 methylation are not tightly coupled.


2006 ◽  
Vol 26 (8) ◽  
pp. 3135-3148 ◽  
Author(s):  
Hongfang Qiu ◽  
Cuihua Hu ◽  
Chi-Ming Wong ◽  
Alan G. Hinnebusch

ABSTRACT The Paf1 complex (Paf1C) interacts with RNA polymerase II (Pol II) and promotes histone methylation of transcribed coding sequences, but the mechanism of Paf1C recruitment is unknown. We show that Paf1C is not recruited directly by the activator Gcn4p but is dependent on preinitiation complex assembly and Ser5 carboxy-terminal domain phosphorylation for optimal association with ARG1 coding sequences. Importantly, Spt4p is required for Paf1C occupancy at ARG1 (and other genes) and for Paf1C association with Ser5-phosphorylated Pol II in cell extracts, whereas Spt4p-Pol II association is independent of Paf1C. Since spt4Δ does not reduce levels of Pol II at ARG1, Ser5 phosphorylation, or Paf1C expression, it appears that Spt4p (or its partner in DSIF, Spt5p) provides a platform on Pol II for recruiting Paf1C following Ser5 phosphorylation and promoter clearance. spt4Δ reduces trimethylation of Lys4 on histone H3, demonstrating a new role for yeast DSIF in promoting a Paf1C-dependent function in elongation.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1734-1734 ◽  
Author(s):  
Christopher R. Vakoc ◽  
Sean A. Mandat ◽  
Ben A. Olenschock ◽  
Gerd A. Blobel

Abstract Epigenetic regulation of gene expression plays a fundamental role during tissue specification and cellular memory. Cells that are committed to a given lineage, for example during hematopoiesis, “remember” their phenotype throughout successive rounds of cell division, reflecting alterations in chromatin structure at genes that are permanently activated or silenced. Cellular memory is anchored in specific sets of histone modifications, which together form the basis for the histone code. This is illustrated in the methylation of histone molecules: while methylation of histone H3 on lysines 4, 36, and 79 is linked with gene activation, methylation of H3 on lysines 9 and 27 and histone H4 on lysine 20 is associated with transcriptionally silent heterochromatin and repressed genes within euchromatin. Not surprisingly, dysregulation of histone methylation contributes to human diseases such as leukemias. Here we examined the methylation of histone molecules during gene activation and repression triggered by the hematopoietic transcription factor GATA-1. Surprisingly, we found that during activation by GATA-1 in erythroid cells, the levels of H3K9 di- and tri-methylation increase dramatically at all examined GATA-1-stimulated genes, including alpha- and beta-globin, AHSP, Band 3 and Glycophorin A. In contrast, at all GATA-1-repressed genes examined (GATA-2, c-kit, and c-myc) these marks are rapidly lost. Peaks of H3K9 methylation were observed in the transcribed portion of genes with lower signals at the promoter regions. Heterochromatin Protein 1γ (HP1γ), a protein containing a chromo-domain that recognizes H3K9 methylation, is also present in the transcribed region of all active genes examined. We extended these analyses to include numerous genes in diverse cell types (primary erythroid cells, primary T-lymphoid cells, epithelial cells and fibroblast) and consistently found a tight correlation between H3K9 methylation and gene activity, highlighting the general nature of our findings. Both the presence of HP1γ and H3K9 methylation at active genes are dependent upon transcription elongation by RNA polymerase II. Finally, HP1γ is in a physical complex with the elongating form of RNA polymerase II. Together, our results show that H3K9 methylation and HP1γ not only function in repressive chromatin, but play a novel and unexpected role during transcription activation. These results further elucidate new combinations of histone modifications that distinguish between repressed and actively transcribing chromatin.


PLoS Genetics ◽  
2016 ◽  
Vol 12 (1) ◽  
pp. e1005758 ◽  
Author(s):  
David Reynolds ◽  
Brigitte T. Hofmeister ◽  
Laura Cliffe ◽  
Magdy Alabady ◽  
T. Nicolai Siegel ◽  
...  

2016 ◽  
Vol 291 (40) ◽  
pp. 21195-21207 ◽  
Author(s):  
Anish Sathianathan ◽  
Priyadarshini Ravichandran ◽  
Jake M. Lippi ◽  
Leah Cohen ◽  
Angelo Messina ◽  
...  

2021 ◽  
Author(s):  
Hayato Hirai ◽  
Yuki Shogaki ◽  
Masamitsu Sato

Centromeres are established by nucleosomes containing the histone H3 variant CENP-A. CENP-A is recruited to centromeres by the Mis18-HJURP machinery. During mitosis, CENP-A recruitment ceases, implying the necessity of CENP-A maintenance at centromeres, although the exact underlying mechanism remains elusive. Herein, we show that the kinetochore protein Mis6 (CENP-I) retains CENP-A during mitosis in fission yeast. Eliminating Mis6 during mitosis caused immediate loss of pre-existing CENP-A at centromeres. CENP-A loss occurred due to the transcriptional upregulation of non-coding RNAs at the central core region of centromeres, as confirmed by the observation RNA polymerase II inhibition preventing CENP-A loss from centromeres in the mis6 mutant. Thus, we concluded that Mis6 blocks the indiscriminate transcription of non-coding RNAs at the core centromere, thereby retaining the epigenetic inheritance of CENP-A during mitosis.


2005 ◽  
Vol 25 (21) ◽  
pp. 9447-9459 ◽  
Author(s):  
Bhargavi Rao ◽  
Yoichiro Shibata ◽  
Brian D. Strahl ◽  
Jason D. Lieb

ABSTRACT Set2p, which mediates histone H3 lysine 36 dimethylation (H3K36me2) in Saccharomyces cerevisiae, has been shown to associate with RNA polymerase II (RNAP II) at individual loci. Here, chromatin immunoprecipitation-microarray experiments normalized to general nucleosome occupancy reveal that nucleosomes within open reading frames (ORFs) and downstream noncoding chromatin were highly dimethylated at H3K36 and that Set2p activity begins at a stereotypic distance from the initiation of transcription genome-wide. H3K36me2 is scarce in regions upstream of divergently transcribed genes, telomeres, silenced mating loci, and regions transcribed by RNA polymerase III, providing evidence that the enzymatic activity of Set2p is restricted to its association with RNAP II. The presence of H3K36me2 within ORFs correlated with the “on” or“ off” state of transcription, but the degree of H3K36 dimethylation within ORFs did not correlate with transcription frequency. This provides evidence that H3K36me2 is established during the initial instances of gene transcription, with subsequent transcription having at most a maintenance role. Accordingly, newly activated genes acquire H3K36me2 in a manner that does not correlate with gene transcript levels. Finally, nucleosomes dimethylated at H3K36 appear to be refractory to loss from highly transcribed chromatin. Thus, H3K36me2, which is highly conserved throughout eukaryotic evolution, provides a stable molecular mechanism for establishing chromatin context throughout the genome by distinguishing potential regulatory regions from transcribed chromatin.


Sign in / Sign up

Export Citation Format

Share Document