The regulation of Caspase 8 chIP-seq motifs mRNA expression DNA methylation

Gene Abstracts from Online databases

Mechanisms of Deregulation of Caspase-8 in Cancers – Caspase 8 mutation/SNPs in head and neck carcinoma, colorectal and gastric cancer – Epigenetic silencing of Caspase 8 in pediatric cancers such as neuroblastoma, etc. – Caspase 8 dom. neg. alternative splicing in leukemia and neuroblastoma – Posttranslational changes, inhibitory phosphorylation

Mutations in Caspase 8

The regulation of Caspase 8 Caspase-8 belongs to the family of cysteine proteases that plays a critical role in the regulation of programmed cell death (apoptosis) 1. Examine chIP seq and DNA methylation data -- UCSC Genome Browser -- ~80 TFBS from the ENCODE project 2. TRANSFAC Database from BioBase -- evaluate the 80 TFBS proposed by ENCODE 3. Microarray data - Expression data -- Find genes co-regulated with Caspase 8

The ENCODE Project: 30 papers -- Produced a massive influx of data on DNA elements/gene regulation 8.4 million DNA recognition motifs, transcription wiring diagram 4061 data sets; 72 cell lines; 119 transcription factors

Determining Caspase 8 regulators chIP-seq currently a preferred technique UCSC browser: look for Caspase 8 5’UTR & promoter Position: chr2:202,098, ,152,434 Size: 54,269 Total Exon Count: 10 Strand: + Promoter: chr2: Question: Could SNPs effect Caspase 8 TFBS?

Copyright OpenHelix. No use or reproduction without express written consent 9 A Sample of the UCSC Genome Browser Annotation Tracks reference sequence comparisons gene details SNPs

Copyright OpenHelix. No use or reproduction without express written consent 10 Overview of the Whole Genome Browser Page (2009 Human Assembly) } Genome viewer mRNA and EST Tracks Expression (such as microarray) Comparative Genomics As a group Individual species Variation and Repeats (including SNPs, copy number variation) Groups of data (Tracks) Mapping and Sequencing Tracks Genes and Gene Prediction Tracks (including sno/miRNA data) Phenotype and Disease Tracks Regulation (including TFBS, methyl from ENCODE) Track data may be updated

Table Browser: Make a track intersection Casp8 Promoter coordinates ENCODE chIP-seq data set

Export from UCSC as BED or FASTA file

Indel rs is protective for cancers chIP seq data goes down page…

The Epigenetics of Caspase 8: DNA methylation

ENCODE has more methylation data

CASP8 promter methylation data

Table Browser: Make a track intersection Casp8 Promoter coordinates ENCODE Bisulfite-seq data set

MATCH tool searches promoter

Caspase 8 Promoter Sequence Analysis TRANSFAC Finds 72 good quality targets for TFs

ENCODE: Casp8 Exon expression by RNA-seq

Oncomine: Caspase8 Co-expressed genes

Coxpresdb.jp – co-expressed genes Based on public Affymetrix array data

IPA: Caspase 8 co-expression networks

IPA: Co- expression network of Casp8

Caspase 8 Regulation Summary UCSC browser contains readily accessible ENCODE and SNP data for cancer studies TRANSFAC can help evaluate chIP-seq data Co-expressed genes and gene set enrichment suggest biological functions