alterations to the transactivation domain of hif - 1 alpha demonstrate this domain contains structures necessary for hypoxia - inducible transactivation , oxygen - dependent degradation , and vhl - hif - 1 alpha interaction . hif - 1 alpha sequences with alterations of the n - tad domain , fragments and analogs thereof are useful in modifying or regulating the activity of bioentities . agonists and antagonists of the n - tad domain of hif - 1 alpha are also useful in modifying or regulating the activity of bioentities .