scholarly journals Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs

2016 ◽  
Author(s):  
Marta Melé ◽  
Kaia Mattioli ◽  
William Mallard ◽  
David M Shechner ◽  
Chiara Gerhardinger ◽  
...  

ABSTRACTWhile long intergenic noncoding RNAs (lincRNAs) and mRNAs share similar biogenesis pathways, these transcript classes differ in many regards. LincRNAs are less evolutionarily conserved, less abundant, and more tissue-specific, suggesting that their pre‐ and post-transcriptional regulation is different from that of mRNAs. Here, we perform an in-depth characterization of the features that contribute to lincRNA regulation in multiple human cell lines. We find that lincRNA promoters are depleted of transcription factor (TF) binding sites, yet enriched for some specific factors such as GATA and FOS relative to mRNA promoters. Surprisingly, we find that H3K9me3—a histone modification typically associated with transcriptional repression—is more enriched at the promoters of active lincRNA loci than at those of active mRNAs. Moreover, H3K9me3-marked lincRNA genes are more tissue-specific. The most discriminant differences between lincRNAs and mRNAs involve splicing. LincRNAs are less efficiently spliced, which cannot be explained by differences in U1 binding or the density of exonic splicing enhancers, but may be partially attributed to lower U2AF65 binding and weaker splicing–related motifs. Conversely, the stability of lincRNAs and mRNAs is similar, differing only with regard to the location of stabilizing protein binding sites. Finally, we find that certain transcriptional properties are correlated with higher evolutionary conservation in both DNA and RNA motifs, and are enriched in lincRNAs that have been functionally characterized.

2018 ◽  
Author(s):  
E. Shannon Torres ◽  
Roger B. Deal

ABSTRACTPlants adapt to changes in their environment by regulating transcription and chromatin organization. The histone H2A variant H2A.Z and the SWI2/SNF2 ATPase BRAHMA have overlapping roles in positively and negatively regulating environmentally responsive genes in Arabidopsis, but the extent of this overlap was uncharacterized. Both have been associated with various changes in nucleosome positioning and stability in different contexts, but their specific roles in transcriptional regulation and chromatin organization need further characterization. We show that H2A.Z and BRM act both cooperatively and antagonistically to contribute directly to transcriptional repression and activation of genes involved in development and response to environmental stimuli. We identified 8 classes of genes that show distinct relationships between H2A.Z and BRM and their roles in transcription. We found that H2A.Z contributes to a range of different nucleosome properties, while BRM stabilizes nucleosomes where it binds and destabilizes and/or repositions flanking nucleosomes. H2A.Z and BRM contribute to +1 nucleosome destabilization, especially where they coordinately regulate transcription. We also found that at genes regulated by both BRM and H2A.Z, both factors overlap with the binding sites of light-regulated transcription factors PIF4, PIF5, and FRS9, and that some of the FRS9 binding sites are dependent on H2A.Z and BRM for accessibility. Collectively, we comprehensively characterized the antagonistic and cooperative contributions of H2A.Z and BRM to transcriptional regulation, and illuminated their interrelated roles in chromatin organization. The variability observed in their individual functions implies that both BRM and H2A.Z have more context-specific roles within diverse chromatin environments than previously assumed.


2005 ◽  
Vol 187 (3) ◽  
pp. 912-922 ◽  
Author(s):  
Jack S. Ikeda ◽  
Anuradha Janakiraman ◽  
David G. Kehres ◽  
Michael E. Maguire ◽  
James M. Slauch

ABSTRACT Salmonella enterica serovar Typhimurium has two manganese transport systems, MntH and SitABCD. MntH is a bacterial homolog of the eukaryotic natural resistance-associated macrophage protein 1 (Nramp1), and SitABCD is an ABC-type transporter. Previously we showed that mntH is negatively controlled at the transcriptional level by the trans-acting regulatory factors, MntR and Fur. In this study, we examined the transcriptional regulation of sitABCD and compared it to the transcriptional regulation of mntH by constructing lacZ fusions to the promoter regions with and without mutations in putative MntR and/or Fur binding sites. The presence of Mn caused transcriptional repression of the sitABCD and mntH promoters primarily via MntR, but Fur was also capable of some repression in response to Mn. Likewise, Fe in the medium repressed transcription of both sit and mntH primarily via Fur, although MntR was also involved in this response. Transcriptional control by MntR and Fur was disrupted by site-specific mutations in the putative MntR and Fur binding sites, respectively. Transcription of the sit operon was also affected by the oxygen level and growth phase, but the increased expression observed under high oxygen conditions and higher cell densities is consistent with decreased availability of metals required for repression by the metalloregulatory proteins.


Oncotarget ◽  
2017 ◽  
Vol 8 (28) ◽  
pp. 46006-46019 ◽  
Author(s):  
Hui Zhao ◽  
Siqi Wang ◽  
Lixia Guo ◽  
Yanli Du ◽  
Linlin Liu ◽  
...  

Blood ◽  
2012 ◽  
Vol 119 (2) ◽  
pp. 388-398 ◽  
Author(s):  
Yongsheng Huang ◽  
Kajal Sitwala ◽  
Joel Bronstein ◽  
Daniel Sanders ◽  
Monisha Dandekar ◽  
...  

The clustered homeobox proteins play crucial roles in development, hematopoiesis, and leukemia, yet the targets they regulate and their mechanisms of action are poorly understood. Here, we identified the binding sites for Hoxa9 and the Hox cofactor Meis1 on a genome-wide level and profiled their associated epigenetic modifications and transcriptional targets. Hoxa9 and the Hox cofactor Meis1 cobind at hundreds of highly evolutionarily conserved sites, most of which are distant from transcription start sites. These sites show high levels of histone H3K4 monomethylation and CBP/P300 binding characteristic of enhancers. Furthermore, a subset of these sites shows enhancer activity in transient transfection assays. Many Hoxa9 and Meis1 binding sites are also bound by PU.1 and other lineage-restricted transcription factors previously implicated in establishment of myeloid enhancers. Conditional Hoxa9 activation is associated with CBP/P300 recruitment, histone acetylation, and transcriptional activation of a network of proto-oncogenes, including Erg, Flt3, Lmo2, Myb, and Sox4. Collectively, this work suggests that Hoxa9 regulates transcription by interacting with enhancers of genes important for hematopoiesis and leukemia.


PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e84203 ◽  
Author(s):  
Mohamed Zouine ◽  
Yongyao Fu ◽  
Anne-Laure Chateigner-Boutin ◽  
Isabelle Mila ◽  
Pierre Frasse ◽  
...  

2014 ◽  
Vol 707 ◽  
pp. 117-120
Author(s):  
Hui Min Li ◽  
Zhi Gang Yang ◽  
Dan Chen

Most of studies on transcriptional regulation mainly focus on upstream regions of genes. More and more recent researches indicate that introns may have important biological functions in transcription regulation of genes. The characterization of words in DNA sequences can be facilitated by the sequences’ functions. Using U-score and Z-score statistic, respectively, we extracted some over-represented words in intron 1s of ribosomal protein genes. A majority of them are accordance with known transcriptional factor binding sites and are potential regulatory elements. And, the detected over-represented words are more likely to form wider potential sequences and are denser in intron 1s of RP genes. We speculate the properties of these words may be associated with the transcriptional regulation of RP genes.


PLoS ONE ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. e0213206 ◽  
Author(s):  
Andres Mejias ◽  
Sergio Diez-Hermano ◽  
Maria D. Ganfornina ◽  
Gabriel Gutierrez ◽  
Diego Sanchez

1997 ◽  
Vol 17 (8) ◽  
pp. 4830-4841 ◽  
Author(s):  
L F Pemberton ◽  
G Blobel

Transcription is regulated by the complex interplay of repressors and activators. Much of this regulation is carried out by, in addition to gene-specific factors, complexes of more general transcriptional modulators. Here we present the characterization of a novel family of transcriptional regulators in yeast. Wtm1p (WD repeat-containing transcriptional modulator) was identified as a protein present in a large nuclear complex. This protein has two homologs, Wtm2p and Wtm3p, which probably arose by gene duplications. Deletion of these genes affects transcriptional repression at several loci, including derepression of IME2, a meiotic gene normally repressed in haploid cells. Targeting of these proteins to DNA resulted in a dramatic repression of activated transcription. In common with a mutation in the histone deacetylase RPD3, wtm mutants showed increased repression at the silent mating-type locus, HMR, and at telomeres. Although all three Wtm proteins could act as transcriptional repressors, Wtm3p, which is the least homologous, appeared to have functions separate from those of the other two. Wtm3p did not appear to be complexed with the other two proteins, was essential for IME2 repression, and could not efficiently repress transcription in the absence of the other Wtm proteins. These data suggested that Wtm1p and Wtm2p are repressors and that Wtm3p has different effects on transcription at different loci.


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