Regulation of Gene Expression 13 February, 2013 Ansuman Chattopadhyay, PhD Head, Molecular Biology Information Services Health Sciences Library System University of Pittsburgh [email protected]
Mar 28, 2015
Regulation of Gene Expression
13 February, 2013
Ansuman Chattopadhyay, PhDHead, Molecular Biology Information ServicesHealth Sciences Library SystemUniversity of [email protected]
Topics
retrieve promoter sequences
determine transcription factor occupancy
browse through the epigenetic biochemical markers
Histone modifications, DNA methylation etc.,
-predict the location of enhancers, silencers and promoters
Major Topics
identify microRNA that have been reported or predicted to interact with a gene
Tools identify promoter sequence(s) present in your gene of interest
Biobase Transpro UCSC genome browser
predict transcription factor binding sites Transfac (Biobase Match)
Browse through the epigenomic markers ENCODE Human Epigenome Atlas
identify miRNA that have been reported or predicted to interact with a gene Mirtarbase Mirbase
http://www.hsls.pitt.edu/guides/genetics
An excellent movie on transcription
http://www.hsls.pitt.edu/guides/genetics
http://vcell.ndsu.edu/animations/transcription/index.htm
Promoter, Enhancer and Silencer
Source: http://www.cbs.dtu.dk/dtucourse/cookbooks/dave/Lekt03bkg.html
http://www.hsls.pitt.edu/guides/genetics
More Movies @ HSLS MolBio Videoshttp://www.hsls.pitt.edu/molbio/videos
Retrieve promoter sequence for a gene
Promoter Sequence
Generic Promoter Seq UCSC Genome Browser
Human Curated Promoter Seq Biobase TransPro mPROMDB CSH TRED Eukaryotic Promoter Database (EPD)
http://www.hsls.pitt.edu/guides/genetics
http://www.hsls.pitt.edu/molbio
Link to the video tutorial:http://media.hsls.pitt.edu/media/clres2705/sequence.swf
http://media.hsls.pitt.edu/media/clres2705/sequence_2.swf
Resources
UCSC Genome Browser: http://genome.ucsc.edu/NCBI Entrez Gene: http://www.ncbi.nlm.nih.gov/gene
Find sequence information for a gene
-genomic -promoter - intron-exon coordinates-mRNA -protein
Fetching Promoters
http://www.hsls.pitt.edu/molbio/videos/play?v=37
Find Promoter Sequence Retrieve promoter sequence for :
Human : BCL2, EGFR C. elegans : let-23 Drosophila: son of sevenless Yeast: fus3
Tips: Go to UCSC genome browser Search by gene name Click on UCSC genes/Wormbase genes/Flybase genes Click on Genomic sequence
http://www.hsls.pitt.edu/guides/genetics
http://goo.gl/3JnmO
Transcription Start Site (TSS)
http://www.hsls.pitt.edu/guides/genetics
Epigenome andEncyclopedia of DNA
Elements Project
Spatiotemporal gene expression
TP53
EGFR
A movie on regulated transcription
http://vcell.ndsu.edu/animations/regulatedtranscription/index.htm
Epigenetic mechanisms
Source: NCBIhttp://www.ncbi.nlm.nih.gov/books/NBK45788/#epi_sci_bkgrd.About_Epigenetics
Genome in 3D
http://www.nature.com/nature/journal/v470/n7333/pdf/470289a.pdf
Chromatin Immuno-Precititation-Seq(ChIP-Seq)
Epigenetic MarkersLandmark Paper:
http://www.nature.com/ng/journal/v39/n3/full/ng1966.html
Histone Modifications
http://goo.gl/GQ9V8
http://www.hsls.pitt.edu/guides/genetics
ENCODE Project
http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001046
Encode Cell Types
http://genome.ucsc.edu/ENCODE/cellTypes.html
Promoter Database
http://www.hsls.pitt.edu/guides/genetics
search.HSLS.MolBio http://search.hsls.pitt.edu/vivisimo/cgi-bin/query-meta?query=promoter+database&input-form=si
mple&v:sources=OBRCandBioMedCentral&v:project=BioInfoTools&submit=Search
Promoter Database
Biobase Knowledge LibraryPromoter report
http://www.hsls.pitt.edu/guides/genetics
http://www.hsls.pitt.edu/molbio
Link to the video tutorial:http://media.hsls.pitt.edu/media/clres2705/biobase.swf
Resources
Biobase Transpro:
Retrieve experimentally verified promoter sequence of a gene i.e. EGFR . What transcription factors binding sites are reported to be present in the gene regulatory region ?
What transcription factors bind to a
promoter sequence?
Find Transcription Factor Binding SitesBasic Search:
TESS (Transcription Element Search System) BIOBASE Match
Phylogenetic Footprinting: ConSite
http://asp.ii.uib.no:8090/cgi-bin/CONSITE/consite
Footer http://biodev.hgen.pitt.edu/footer_php/Footerv2_0.php
http://www.hsls.pitt.edu/guides/genetics
Transcription Factors (TF)
Database: Transfac-BioBase https://portal.biobase-international.com/cgi-bin/build_ghptywl/idb/1.0/searchengine/start.cgi
Classification https://portal.biobase-international.com/cgi-bin/build_ghptywl/idb/1.0/searchengine/start.cgi
Properties Binding sites Matrix https://portal.biobase-international.com/cgi-bin/build_ghptywl/idb/1.0/searchengine/start.cgi
Transcription Factors
Transcription Factor
http://www.cisreg.ca/cgi-bin/tfe/home.pl
Transcription Factor binding sites
Jonathan M. Keith (ed.), Bioinformatics, Volume II: Structure, Function and Applications, vol. 453, © 2008 Humana Press,
http://www.hsls.pitt.edu/guides/genetics
Information pertaining to a transcription factor
http://www.hsls.pitt.edu/molbio/videos/play?v=74
Transcription Factors occupancy analysis Retrieve potential promoter sequence and
predict transcription factors binding sites present in the promoter region:
http://media.hsls.pitt.edu/media/clres2705/match.swf
http://www.hsls.pitt.edu/guides/genetics
http://www.hsls.pitt.edu/molbio
Link to the video tutorial:http://media.hsls.pitt.edu/media/clres2705/match.swf
Resources
Biobase Match: https://portal.biobase-international.com/cgi-bin/build_ghptywl/idb/1.0/searchengine/start.cgi
Retrieve potential promoter sequence of a yeast gene, fus3 and predict transcription factors binding sites present in the promoter region.
Use Biobase Match program
http://www.hsls.pitt.edu/molbio/videos/play?v=47
Find conserved transcription factor binding sites• Footer
• http://biodev.hgen.pitt.edu/footer_php/Footerv2_0.php
• VISTA Tools• http://genome.lbl.gov/vista/index.shtml
• rVISTA• http://genome.lbl.gov/vista/rvista/submit.shtml
• Whole Genome rVISTA• http://genome-test.lbl.gov/cgi-bin/WGRVistaInputCommon.pl
Footer Result Page
http://www.hsls.pitt.edu/guides/genetics
Browsing the ENCODE Data
Sec61g and EGFR
human chr7:54,801,956-55,305,954
EGFR and Sec61g
Role of the Sec61 translocon in EGF receptor trafficking to the nucleus and gene expression.Liao HJ, Carpenter G.
Mol Biol Cell. 2007 Mar;18(3):1064-72. Epub 2007 Jan 10.
http://www.hsls.pitt.edu/guides/genetics
http://www.hsls.pitt.edu/molbio
Link to the video tutorial:http://media.hsls.pitt.edu/media/clres2705/ucsc_convert.swfFile: UCSC_convert.swf
Resource
UCSC Genome Browser: http://genome.ucsc.edu/
Convert the human genomic region between genes sec61g and EGFR into mouse, rat and zebra fish genomes
UCSC Genome Browser: Navigating a Genomic Region
http://www.hsls.pitt.edu/guides/genetics
UCSC Genome Browser: Navigating a Genomic Region
http://www.hsls.pitt.edu/guides/genetics
UCSC Genome Browser: Navigating a Genomic Region
What transcription factors bind in this region?
http://www.hsls.pitt.edu/guides/genetics
Sec61g and EGFR
http://www.hsls.pitt.edu/molbio
Link to the video tutorial:http://media.hsls.pitt.edu/media/molbiovideos/encode1-ac0212.swfhttp://media.hsls.pitt.edu/media/molbiovideos/encode2-ac0212.swfhttp://media.hsls.pitt.edu/media/molbiovideos/encode3-ac0212.swf
Resource
UCSC Genome Browser: http://genome.ucsc.edu/
Identify promoter, enhancer and silencer sequences by browsing the epigenomic markers generated by the ENCODE project
Cell Lines
K562
NHLF
Human Epigenome Atlas:
http://www.genboree.org/epigenomeatlas/edaccGridViewerPublic.rhtml
Regulome
Retrieve MicroRNA target genes
MicroRNA Biology http://hstalks.com/main/search_bar.php?s=microRNA&l=252&k=TALK
http://www.hsls.pitt.edu/molbio
http://www.hsls.pitt.edu/molbio
Link to the video tutorial:http://media.hsls.pitt.edu/media/clres2705/mirna.swf
Resources
MiRNA database• Mirbase: http://www.mirbase.org Target database• Mirtarbase: http://mirtarbase.mbc.nctu.edu.tw/• Targetscan: http://www.targetscan.org/• Miranda: http://www.microrna.org/• Pictar: http://pictar.mdc-berlin.de/
• Identify miRNA(s) that have been reported or predicted to interact with a gene.
• Retrieve target genes of a miRNA
Result comparison of miRNA prediction algorithms
http://www.hsls.pitt.edu/molbio
ExprTarget: An Integrative Approach to Predicting Human MicroRNA Targets
PLOs One http://www.plosone.org/article/info:doi/10.1371/journal.pone.0013534
Thank you!Any questions?
Carrie Iwema Ansuman [email protected] [email protected] 412-383-6887 412-648-1297
http://www.hsls.pitt.edu/guides/genetics