lac A. Negative regulators are regulatory elements which obstruct the binding of RNA polymerase to the promoter region, thus repressing transcription. In terms of the lac operon, the negative regulator would be the lac repressor which binds to the promoter in the same site that RNA polymerase normally binds. The binding of the lac repressor to RNA polymerase's binding site inhibits the transcription of the lac genes. Only when a corepressor is bound to the lac repressor will the binding site be free for RNA polymerase to carry out transcription of the lac genes. Gene regulatory elements Promoters reside at the beginning of the gene and serve as the site where the transcription machinery assembles and transcription of the gene begins. Enhancers turn on the promoters at specific locations, times, and levels and can be simply defined as the “promoters of the promoter.” Silencers are thought to turn off gene expression at specific time points and locations. Insulators, also called boundary elements, are DNA sequences that create cis-regulatory boundaries that prevent the regulatory elements of one gene from affecting neighboring genes. The general dogma is that these regulatory elements get activated by the binding of transcription factors, proteins that bind to specific DNA sequences, and control mRNA transcription. There could be several transcription factors that need to bind to one regulatory element in order to activate it. In addition, several other proteins, called transcription cofactors, bind to the transcription factors themselves to control transcription. Negative regulators Negative regulators act to prevent transcription or translation. Examples such as cFLIP suppress cell death mechanisms leading to pathological disorders like cancer, and thus play a crucial role in drug resistance. Circumvention of such actors is a challenge in cancer therapy. Negative regulators of cell death in cancer include cFLIP, Bcl2 family, Survivin, HSP, IAP, NF-κB, Akt, mTOR, and FADD. Detection There are several different techniques to detect regulatory genes, but of the many there are a certain few that are used more frequently than others. One of these select few is called ChIP-chip. ChIP-chip is an in vivo technique used to determine genomic binding sites for transcription factors in two component system response regulators. In vitro microarray based assay (DAP-chip) can be used to determine gene targets and functions of two component signal transduction systems. This assay takes advantage of the fact that response regulators can be phosphorylated and thus activated in vitro