scholarly journals Discovery of directional chromatin-associated regulatory motifs affecting human gene transcription

2018 ◽  
Author(s):  
Naoki Osato

AbstractBackgroundChromatin interactions are essential in enhancer-promoter interactions (EPIs) and transcriptional regulation. CTCF and cohesin proteins located at chromatin interaction anchors and other DNA-binding proteins such as YY1, ZNF143, and SMARCA4 are involved in chromatin interactions. However, there is still no good overall understanding of proteins associated with chromatin interactions and insulator functions.ResultsHere, I describe a systematic and comprehensive approach for discovering DNA-binding motifs of transcription factors (TFs) that affect EPIs and gene expression. This analysis identified 96 biased orientations [64 forward-reverse (FR) and 52 reverse-forward (RF)] of motifs that significantly affected the expression level of putative transcriptional target genes in monocytes, T cells, HMEC, and NPC and included CTCF, cohesin (RAD21 and SMC3), YY1, and ZNF143; some TFs have more than one motif in databases; thus, the total number is smaller than the sum of FRs and RFs. KLF4, ERG, RFX, RFX2, HIF1, SP1, STAT3, and AP1 were associated with chromatin interactions. Many other TFs were also known to have chromatin-associated functions. The predicted biased orientations of motifs were compared with chromatin interaction data. Correlations in expression level of nearby genes separated by the motif sites were then examined among 53 tissues.ConclusionOne hundred FR and RF orientations associated with chromatin interactions and functions were discovered. Most TFs showed weak directional biases at chromatin interaction anchors and were difficult to identify using enrichment analysis of motifs. These findings contribute to the understanding of chromatin-associated motifs involved in transcriptional regulation, chromatin interactions/regulation, and histone modifications.

2020 ◽  
Author(s):  
JOUNG SUG KIM ◽  
SongHwa Chae ◽  
Kyong Mi Jun ◽  
Gang-Seob Lee ◽  
Jong-Seong Jeon ◽  
...  

Abstract BackgroundTranscription factors (TFs) regulate the expression of genes at the transcriptional level by binding a specific DNA sequence. Thus, predicting the DNA-binding motifs of TFs is one of the most important areas for the functional analysis of TFs in the postgenomic era. Although many methods have been developed for this challenge, there are still many TFs with unknown DNA-binding motifs.FindingsIn this paper, we designed an rice (Oryza sativa)-specific protein binding microarray (RPBM), and its probes are 40 bp long with 20 bp of overlap; there are 49 probes spanning the 1 kb promoter region before the translation start site of each gene. To confirm the efficiency of RPBM technology, we selected two TFs, OsWOX13 and OsSMF1. We identified the ATTGATTG DNA-binding sequence and 635 putative target genes of OsWOX13. OsSMF1 bound to GCTGACTCA and GGATGCC sequences and bound especially strongly to CCACGTCA. A total of 932 putative target genes were identified for OsSMF1.ConclusionsRPBM can be applicable in the analysis of DNA-binding motifs for TFs where binding is evaluated in extended natural promoter regions. The analysis can also be applicable to TFs that have single or multiple binding motifs. The technology might even be expanded for application to TFs that are heterodimers or form higher-order complexes.


Planta ◽  
2021 ◽  
Vol 253 (2) ◽  
Author(s):  
Joung Sug Kim ◽  
SongHwa Chae ◽  
Kyong Mi Jun ◽  
Gang-Seob Lee ◽  
Jong-Seong Jeon ◽  
...  

Abstract Main conclusion The present study showed that a rice (Oryza sativa)-specific protein-binding microarray (RPBM) can be applied to analyze DNA-binding motifs with a TF where binding is evaluated in extended natural promoter regions. The analysis may facilitate identifying TFs and their downstream genes and constructing gene networks through cis-elements. Abstract Transcription factors (TFs) regulate gene expression at the transcriptional level by binding a specific DNA sequence. Thus, predicting the DNA-binding motifs of TFs is one of the most important areas in the functional analysis of TFs in the postgenomic era. Although many methods have been developed to address this challenge, many TFs still have unknown DNA-binding motifs. In this study, we designed RPBM with 40-bp probes and 20-bp of overlap, yielding 49 probes spanning the 1-kb upstream region before the translation start site of each gene in the entire genome. To confirm the efficiency of RPBM technology, we selected two previously studied TFs, OsWOX13 and OsSMF1, and an uncharacterized TF, OsWRKY34. We identified the ATTGATTG and CCACGTCA DNA-binding sequences of OsWOX13 and OsSMF1, respectively. In total, 635 and 932 putative feature genes were identified for OsWOX13 and OsSMF1, respectively. We discovered the CGTTGACTTT DNA-binding sequence and 195 putative feature genes of OsWRKY34. RPBM could be applicable in the analysis of DNA-binding motifs for TFs where binding is evaluated in the promoter and 5′ upstream CDS regions. The analysis may facilitate identifying TFs and their downstream genes and constructing gene networks through cis-elements.


Cell ◽  
1991 ◽  
Vol 65 (7) ◽  
pp. 1267-1279 ◽  
Author(s):  
Anders M. Näär ◽  
Jean-Marle Boutin ◽  
Steven M. Lipkin ◽  
Victor C. Yu ◽  
Jeffrey M. Holloway ◽  
...  

ChemInform ◽  
2010 ◽  
Vol 32 (47) ◽  
pp. no-no
Author(s):  
Shigeki Sasaki ◽  
Takayuki Shibata ◽  
Hidemine Torigoe ◽  
Yosinori Shibata ◽  
Minoru Maeda

2010 ◽  
Vol 107 (38) ◽  
pp. 16506-16511 ◽  
Author(s):  
M. de Vega ◽  
J. M. Lazaro ◽  
M. Mencia ◽  
L. Blanco ◽  
M. Salas

Blood ◽  
1993 ◽  
Vol 81 (5) ◽  
pp. 1124-1131 ◽  
Author(s):  
J Morrissey ◽  
DC Tkachuk ◽  
A Milatovich ◽  
U Francke ◽  
M Link ◽  
...  

Translocations involving chromosome band 11q23 in acute leukemias have recently been shown to involve the HRX gene that codes for a protein with significant similarity to Drosophila trithorax. HRX gene alterations are consistently observed in t(4;11) (q21;q23)-carrying leukemias and cell lines by Southern blot analyses and are accompanied by HRX transcripts of anomalous size on Northern blots. HRX-homologous cDNAs were isolated from a library prepared from t(4;11)-carrying acute leukemia cells. cDNAs representative of transcription products from the derivative 11 chromosome were shown to contain HRX sequences fused to sequences derived from chromosome band 4q21. Fragments of the latter were used to clone and analyze cDNAs for wild-type 4q21 transcripts that predicted a 140-Kd basic protein (named FEL) that is rich in prolines, serines, and charged amino acids. FEL contains guanosine triphosphate-binding and nuclear localization consensus sequences and uses one of two possible 5' exons encoding the first 12 or 5 amino acids. After t(4;11) translocations, 913 C-terminal amino acids of FEL are fused in frame to the N-terminal portion of HRX containing its minor groove DNA binding motifs. These features are similar to predicted t(11;19) fusion proteins, suggesting that HRX consistently contributes a novel DNA-binding motif to at least two different chimeric proteins in acute leukemias.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Colin T. Waters ◽  
Stephen S. Gisselbrecht ◽  
Yuliya A. Sytnikova ◽  
Tiziana M. Cafarelli ◽  
David E. Hill ◽  
...  

AbstractUnderstanding the contributions of transcription factor DNA binding sites to transcriptional enhancers is a significant challenge. We developed Quantitative enhancer-FACS-Seq for highly parallel quantification of enhancer activities from a genomically integrated reporter in Drosophila melanogaster embryos. We investigate the contributions of the DNA binding motifs of four poorly characterized TFs to the activities of twelve embryonic mesodermal enhancers. We measure quantitative changes in enhancer activity and discover a range of epistatic interactions among the motifs, both synergistic and alleviating. We find that understanding the regulatory consequences of TF binding motifs requires that they be investigated in combination across enhancer contexts.


2019 ◽  
Author(s):  
Guoliang Li ◽  
Tongkai Sun ◽  
Huidan Chang ◽  
Liuyang Cai ◽  
Ping Hong ◽  
...  

AbstractUnderstanding chromatin interactions is important since they create chromosome conformation and link the cis- and trans-regulatory elements to their target genes for transcriptional regulation. Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) sequencing is a genome-wide high-throughput technology that detects chromatin interactions associated with a specific protein of interest. Previously we developed ChIA-PET Tool in 2010 for ChIA-PET data analysis. Here we present the updated version of ChIA-PET Tool (V3), is a computational package to process the next-generation sequence data generated from ChIA-PET experiments. It processes the short-read data and long-read ChIA-PET data with multithreading and generates the statistics of results in a HTML file. In this paper, we provide a detailed demonstration of the design of ChIA-PET Tool V3 and how to install it and analyze a specific ChIA-PET data set with it. At present, other ChIA-PET data analysis tools have developed including ChiaSig, MICC, Mango and ChIA-PET2 and so on. We compared our tool with other tools using the same public data set in the same machine. Most of peaks detected by ChIA-PET Tool V3 overlap with those from other tools. There is higher enrichment for significant chromatin interactions of ChIA-PET Tool V3 in APA plot. ChIA-PET Tool V3 is open source and is available at GitHub (https://github.com/GuoliangLi-HZAU/ChIA-PET_Tool_V3/).


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