Transcriptional regulation

Regulation of transcription controls when transcription occurs and how much RNA is created. Transcription of a gene by RNA polymerase can be regulated by at least five mechanisms:
Specificity factors alter the specificity of RNA polymerase for a given promoter or set of promoters, making it more or less likely to bind to them (i.e. sigma factors used in prokaryotic transcription).
Repressors bind to non-coding sequences on the DNA strand that are close to or overlapping the promoter region, impeding RNA polymerase's progress along the strand, thus impeding the expression of the gene.
General transcription factors These transcription factors position RNA polymerase at the start of a protein-coding sequence and then release the polymerase to transcribe the mRNA.
Activators enhance the interaction between RNA polymerase and a particular promoter, encouraging the expression of the gene. Activators do this by increasing the attraction of RNA polymerase for the promoter, through interactions with subunits of the RNA polymerase or indirectly by changing the structure of the DNA.
Enhancers are sites on the DNA helix that are bound to by activators in order to loop the DNA bringing a specific promoter to the initiation complex.
Silencers are regions of DNA that are bound by transcription factors in order to silence gene expression. The mechanism is very similar to that of enhancers.

The Many Facets of NF-Kappa B

NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that acts as a transcription factor. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-κB plays a key role in regulating the immune response to infection. Consistent with this role, incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory.

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NF-κB was first discovered in the lab of Nobel Prize laureate David Baltimore via its interaction with an 11-base pair sequence in the immunoglobulin light-chain enhancer in B cells.

About the Speaker

Baltimore was born in New York City and graduated from Great Neck High School in 1956.He earned a BA at Swarthmore College in 1960, and received his Ph.D. at Rockefeller University in 1964. After postdoctoral fellowships at Massachusetts Institute of Technology (MIT) and Albert Einstein College of Medicine and a non-faculty research position at the Salk Institute, he joined the MIT faculty in 1968.

In 1975, at the age of 37, he shared the Nobel Prize for Physiology or Medicine with Howard Temin and Renato Dulbecco. The citation reads, "for their discoveries concerning the interaction between tumour viruses and the genetic material of the cell." At the time, Baltimore's greatest contribution to virology was his discovery of reverse transcriptase (RTase or RT). Reverse transcriptase is essential for the reproduction of retroviruses such as HIV and was also discovered independently, and at about the same time, by Mizutani and Temin.

Related Link: Nobel Prize lecture