An element regulating adrenal-specific steroid 21-hydroxylase expression is located within the slp gene.

D.S Milstone,S.K Shaw,K.L Parker,M Szyf,J.G Seidman

doi:10.1016/s0021-9258(19)36701-8

D.S Milstone, S.K Shaw + Show 3 more

Open Access

https://doi.org/10.1016/s0021-9258(19)36701-8

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Abstract

In this report we demonstrate that a transcriptional regulatory element for one gene lies within a second, seemingly unrelated gene. Specifically, the 3' portion of the murine sex-limited protein (slp) gene, located within the class III region of the major histocompatibility complex, contains an element that regulates expression of the linked steroid 21-hydroxylase gene. A 4.2-kilobase (kb) major histocompatibility complex region, located between -2.2 and -6.4 kb upstream of 21OH-A, is required for expression of a chloramphenicol acetyltransferase reporter gene in transgenic mice. Two short regions of DNA, located between -5.3 and -6.0 kb, stimulate chloramphenicol acetyltransferase expression in Y1 adrenocortical tumor cells, and both of these active regions lie within the slp gene. A 21-base pair sequence, which is required for activity of the most 3' region, does not contain any of over 100 previously identified transcriptional regulatory elements. This juxtaposition of structural and regulatory elements of otherwise unrelated genes suggests a mechanism by which the evolutionarily conserved genetic linkage of 21OH-A and slp (or the homologous complement component C4) might provide a selective advantage. Analogous genetic arrangements may explain other examples of conserved linkage of disparate genes.

Highlights

In this report we demonstrate thata transcriptional elements that aredistinct from enhancers and arelocated as regulatory element for one genelies within a second, much as 50 kb’ distant from these genes
The predominate glucocorticoidand mineralocorticoid hormones synthesized in the adrenal are characterized by the presence of an hydroxyl group at position 21 of the steroid ring structure.This 21-OH group is added by steroid 21hydroxylase, found at high levels throughout the adrenal and -6.0 kb, stimulate chloramphenicol acetyltrans- cortex
The results demonstrate that additionalelements that regulate 21-OH Gene transcription by RNA polymerase I1 is regulated by expression are located within the structuralportion of the slp cis-acting DNA sequences thatinteract with trans-acting gene. binding proteins to direct the transcriptionalcomplex to the initiation site of the relevant gene.The DNA sequences that mediate these interactions include upstream “promoter” elements, usually located within several hundred base pairs of the transcription initiation site, and “enhancer” elements that can be located either several kilobases 5’ or 3‘ or within an intron of the regulated gene

Summary

Introduction

In this report we demonstrate thata transcriptional elements that aredistinct from enhancers and arelocated as regulatory element for one genelies within a second, much as 50 kb’ distant from these genes. The resulting transgenes contained 210H-A 5”flanking addition, studies of the human globin [2] and CD2 [3] loci sequences fused to the gene for CAT/HSV tk followed by approxiand the chicken lysozyme locus [4] demonstrate regulatory mately 200 bp of pUC-12 at the 3’ end as described below.

Results

Conclusion