The promoter of the human dihydrofolate reductase (DHFR)

TSTRODUCTIONThe l)urpose of this investigation is to explore the basic anatomical niechanisms involved in the types of locomotion performed by iguanid and agamid lizards, both quadrupedal and bipedal. Fundamelitally, all lizards are quadrupeds at any speed, wliether walking or ruiining, but there are a t least 18 species able to employ bipedal locomotion in which the dual functions of body propulsion and support rest solel~7 upon the hindlimbs. These studies indicate the nature of the quantitative differences in inyology and osteology between quadrupedal and bipedal forms.C'onsiderable work has beeii done on the morphology of the pelvis and hindlimb of reptiles, both living and extinct (Gadow, Howell '38; and others), hut relatively little from a functional point of view. Gregory and Camp ( 'lS), Romev ( '22), Nauck ( '24) and Schaeffcr ('41) have treated functional aspects of i~p t i l i a n locomotion ; the most recent, although very general account, is that of Young ('50). Analyses of the actual locoinotor methods employed by recent reptiles (excluding snakes) liare been published on only two crocodilia, Osteolamus (17021 1 THE AXERIC4N J O V R N 4 L OF AYATOaIY, \Old. 95, N O 1 J L L Y 1964 R1CEAI:D C . SXYDEE MATERIAT,S AKD 3IETIIOI)GComparative studies of the osteology a e d nq7olog.y of the pelvis and hiridlimb were made on 12 species of lizards, comprising two families, as indicated in the following list :

No abstract

Specific interactions between DNA and transcription factors are necessary for transcription initiation. These interactions provide a potential target for the selective inhibition of eukaryotic gene expression. Mithramycin is a DNA binding antibiotic which, in the presence of Mg2", binds G-C containing sequences in the minor groove. The SV40 early promoter contains six G-C decanucleotide sequences, which are binding sites for the transcriptional activating factor, Spl. Each of the six Spl binding sites of this promoter is protected from DNAse 1 digestion by mithramycin binding. Mithramycin binding to the G-C rich sequences in the SV40 early promoter prevents subsequent protein binding to these sequences. The gel retardation of the SV40 early promoter fragment incubated with a HeLa cell extract is completely abrogated by pretreatment of the DNA fragment with mithramycin. The functional significance of mithramycin binding is reflected in the ability of mithramycin to block promoter function. Mithramycin inhibits promoter dependent transcription in an in vitro runoff transcription system in a concentration dependent manner. This suggests that mithramycin prevents transcriptional activation of the SV40 early promoter by blocking binding of transcriptional activating proteins to G-C rich promoter regions.