Zinc Transcription Factors

There are many zinc enzymes, but there appear to be even more transcription factors that use zinc. These sites have all been identified in the last 20 years and have been less thoroughly investigated than the zinc enzymes. Variable numbers of zinc atoms are each coordinated by four cysteine/histidine residues to stabilize a DNA binding structure. A search of the human genome has revealed over 1000 genes (about 3% of those identified) containing these characteristic zinc finger domains. An important class of zinc finger transcription factors is the steroid/thyroid receptor superfamily, which is responsible for mediating the biological response to a wide range of hormonal and metabolic signals, including retinoic acid and vitamin D. These factors all have nine conserved cysteine residues in the DNA binding region, eight of which are coordinated by two atoms of zinc. Loss of zinc from these sites would interrupt biological function, but it is not clear that this ever happens in a physiological context. Recently, the new array technologies have been used to assess the genome-wide response to changing zinc availability in different tissues, including intestine, liver, and cells of the immune system.

The gene products that have been identified as zinc sensitive by these approaches amount to about 5% of the expressed genes within a tissue. They do not necessarily encode zinc proteins themselves but rather proteins whose transcription is altered by zinc. MTF-1 is likely to mediate some but not all of these changes, and other transcription factors whose activity is dependent on zinc may soon be found.

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