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Two regulatory domains are required for downregulation of c-myc transcription in differentiating U937 cells.

Abstract：

:In many differentiating cells, a reduction of c-myc proto-oncogene expression is a prerequisite for terminal differentiation. The downmodulation of c-myc in differentiating cells is due to at least two different mechanisms: (i) an elongation block to c-myc transcription activated during an early phase of differentiation and (ii) an inhibition of transcription initiation activated during a later phase. In order to determine cis-acting target structures of the c-myc gene required for the late-phase downregulation of transcriptional initiation, we permanently transfected U937 cells with constructs containing the bacterial chloramphenicol acetyl transferase (CAT) gene driven by a 2.8 kb c-myc promoter region or deletions thereof. We determined two distinct domains in the c-myc promoter region both of which are essential for efficient terminal downregulation: a proximal domain and a distal domain which are located between base pairs -606 to -101, and between -2392 to -1396, respectively, relative to P1. The identification of two distinct regulatory elements suggests the requirement and cooperation of two regulatory factors as an essential event for mediating differentiation-induced downregulation of c-myc in monocytic cells. The implications of these results for deregulation of the translocated c-myc allele in Burkitt's lymphoma are discussed.

journal_name

Oncogene

journal_title

Oncogene

authors

Skerka C,Zipfel PF,Siebenlist U

subject

Has Abstract

pub_date

1993-08-01 00:00:00

pages

2135-43

issue

8

eissn

0950-9232

issn

1476-5594

journal_volume

8

pub_type

杂志文章

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