title: Whole genome expression profiling shows that BRG1 transcriptionally regulates UV inducible genes and other novel targets in human cells.
abstract: UV irradiation is known to cause cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs), and plays a large role in the development of cancer. Tumor suppression, through DNA repair and proper cell cycle regulation, is an integral factor in maintaining healthy cells and preventing development of cancer. Transcriptional regulation of the genes involved in the various tumor suppression pathways is essential for them to be expressed when needed and to function properly. BRG1, an ATPase catalytic subunit of the SWI/SNF chromatin remodeling complex, has been identified as a tumor suppressor protein, as it has been shown to play a role in Nucleotide Excision Repair (NER) of CPDs, suppress apoptosis, and restore checkpoint deficiency, in response to UV exposure. Although BRG1 has been shown to regulate transcription of some genes that are instrumental in proper DNA damage repair and cell cycle maintenance in response to UV, its role in transcriptional regulation of the whole genome in response to UV has not yet been elucidated. With whole genome expression profiling in SW13 cells, we show that upon UV induction, BRG1 regulates transcriptional expression of many genes involved in cell stress response. Additionally, our results also highlight BRG1's general role as a master regulator of the genome, as it transcriptionally regulates approximately 4.8% of the human genome, including expression of genes involved in many pathways. RT-PCR and ChIP were used to validate our genome expression analysis. Importantly, our study identifies several novel transcriptional targets of BRG1, such as ATF3. Thus, BRG1 has a larger impact on human genome expression than previously thought, and our studies will provide inroads for future analysis of BRG1's role in gene regulation.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Leah
authors.initials: L
authors.lastname: Nemzow
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Hu
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Feng
authors.initials: F
authors.lastname: Gong
mesh_terms: D004265:DNA Helicases / Q000502:physiology*; D020869:Gene Expression Profiling; D015894:Genome, Human; D057809:HEK293 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D013312:Stress, Physiological; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation / Q000528:radiation effects*; D059467:Transcriptome; D014466:Ultraviolet Rays
chemical_list: D009687:Nuclear Proteins; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases