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Premature termination of transcription of the murine c-myc gene

Roberts, Sadia; (1993) Premature termination of transcription of the murine c-myc gene. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Premature termination or attenuation of RNA polymerase II transcription has recently been found to regulate expression of a number of genes including the c-myc oncogene, but its mechanism is not understood. By transcribing the c-myc gene in injected Xenopus oocytes, various parameters were altered and their effects on the efficiency of the c-myc T2 attenuator were studied. The attenuator functioned downstream of a variety of promoters. However polymerases situated further from the promoter appear to have a lower ability to recognise the attenuator since termination efficiency declined markedly when it was placed more than 400bp from the start site. Furthermore, only transcription which initiated at the c-myc promoter most proximal to the attenuator (P2) terminated prematurely. Transcription from the P1 promoter terminated at T2 only when the natural distance between P1 and T2 was reduced. Transcription reading through the c-myc attenuator, but not that which terminates, was inhibited by the adenosine analog 5,6-dichloro-1-B-D-ribofuranosylbenzimidazole (DRB). It is proposed that only those elongation complexes which are resistant to DRB are capable of premature termination, and that this subset exists only within the first few hundred bases of the transcription unit. Transcription initiated at the P1 promoter was found to terminate prematurely at two positions, T1A and T1B which flank the P2 TATA box and are thus closer to the P1 promoter than T2. T1B is a T-rich sequence which resembles previously identified attenuation sites but T1A appears to represent a different class of termination site. A 120bp sequence containing T1A induced termination downstream of a heterologous promoter. T1A is located immediately upstream of the P2 TATA box. Mutagenesis of an element overlapping this TATA box affected both the efficiency and the position of termination. A 28bp sequence including this element bound a factor whose sequence specificity correlated with T1A terminator function.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Premature termination of transcription of the murine c-myc gene
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10102528
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