Comment[ArrayExpressAccession] E-GEOD-42523 MAGE-TAB Version 1.1 Public Release Date 2013-07-14 Investigation Title Spatially restricted position-dependent implications of lamin A promoter occupancy on gene activity (expression) Comment[Submitted Name] Spatially restricted position-dependent implications of lamin A promoter occupancy on gene activity (expression) Experiment Description Interactions between the nuclear lamina (NL) and chromatin are thought to occur through large lamin association domains (LADs) and correlate with gene repression in these domains. We show that binding of lamin A/C (LMNA) to promoters occurs on discrete domains that are associated with distinct transcriptional outputs. Chromatin immunoprecipitation identifies thousands of LMNA-bound promoters, primarily linked to signaling functions. LMNA often occupies narrow domains on promoters, yet LMNA-bound promoters are often contiguous. LMNA-bound genes are overall repressed, but repression correlates with co-enrichment in repressive histone marks rather than LMNA occupancy per se. Genes marked by LMNA and H3K4me3 escape LMNA-associated repression in the absence of repressive histone marks. Positioning of LMNA on promoters relative to the TSS correlates with distinct transcriptional outputs: whereas upstream-distal binding can be transcriptionally permissive, TSS occupancy is associated with promoter inactivity. Perturbation in NL organization causes reorganization of lamin promoter occupancy and uncouples LMNA binding from promoter inactivity. Our results show the existence of many spatially restricted LMNA binding events on promoter regions, with distinct position-dependent transcriptional outputs. Total RNA obtained from ASCs and ASCs depleted of LMNA (LMNA-KD) and processed for microarray hybridization. Term Source Name ArrayExpress EFO Term Source File http://www.ebi.ac.uk/arrayexpress/ http://www.ebi.ac.uk/efo/efo.owl Person Last Name Collas Collas Lund Person First Name Philippe P E Person Email geo@ncbi.nlm.nih.gov Person Affiliation University of Oslo Person Address Institute of Basic Medical Sciences, University of Oslo, PO Box 1112 Blindern, Oslo, Norway Person Roles submitter Protocol Name P-GSE42523-1 P-GSE42523-3 P-GSE42523-4 P-GSE42523-2 P-GSE42523-5 Protocol Description The data were normalised using quantile normalisation with GenomeStudio ID_REF = VALUE = quantile normalized Detection Pvalue = Biotinylated cRNA were prepared with the Ambion MessageAmp kit for Illumina arrays Standard Illumina hybridization protocol RNA was extracted with Trizol reagent, followed by clean-up and DNase I treatment with QIAGEN RNeasy mini kit in accordance with the prescribed protocol provided with the kit. Quality control was performed with Agilent Bioanalyser. Standard Illumina scanning protocol Protocol Type normalization data transformation protocol labelling protocol hybridization protocol nucleic acid extraction protocol array scanning protocol Experimental Factor Name CELL TREATMENT Experimental Factor Type cell treatment Comment[SecondaryAccession] GSE42523 Comment[GEOReleaseDate] 2013-07-14 Comment[ArrayExpressSubmissionDate] 2012-11-26 Comment[GEOLastUpdateDate] 2013-07-14 Comment[AEExperimentType] transcription profiling by array Comment[AdditionalFile:Data1] GSE42523_non_normalized.txt SDRF File E-GEOD-42523.sdrf.txt