Oxygen-regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase A genes: similarities with the erythropoietin 3' enhancer.
Production of the glycoprotein hormone erythropoietin (Epo) in response to hypoxic stimuli is almost entirely restricted to particular cells within liver and kidney, yet the transcriptional enhancer lying 3' to the Epo gene shows activity inducible by hypoxia after transfection into a wide vari...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1994
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| _version_ | 1797073610695770112 |
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| author | Firth, J Ebert, B Pugh, C Ratcliffe, P |
| author_facet | Firth, J Ebert, B Pugh, C Ratcliffe, P |
| author_sort | Firth, J |
| collection | OXFORD |
| description | Production of the glycoprotein hormone erythropoietin (Epo) in response to hypoxic stimuli is almost entirely restricted to particular cells within liver and kidney, yet the transcriptional enhancer lying 3' to the Epo gene shows activity inducible by hypoxia after transfection into a wide variety of cultured cells. The implication of this finding is that many cells which do not produce Epo contain a similar, if not identical, oxygen-regulated control system, suggesting that the same system is involved in the regulation of other genes. We report that the human phosphoglycerate kinase 1 and mouse lactate dehydrogenase A genes are induced by hypoxia with characteristics which resemble induction of the Epo gene. In each case expression is induced by cobalt, but not by cyanide, and hypoxic induction is blocked by the protein-synthesis inhibitor cycloheximide. We show that the relevant cis-acting control sequences are located in the 5' flanking regions of the two genes, and we define an 18-bp element in the 5' flanking sequence of the phosphoglycerate kinase 1 gene which is both necessary and sufficient for the hypoxic response, and which has sequence and protein-binding similarities to the hypoxia-inducible factor 1 binding site within the Epo 3' enhancer. |
| first_indexed | 2024-03-06T23:24:30Z |
| format | Journal article |
| id | oxford-uuid:69e70f53-caeb-4478-9c78-e3ba68722407 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:24:30Z |
| publishDate | 1994 |
| record_format | dspace |
| spelling | oxford-uuid:69e70f53-caeb-4478-9c78-e3ba687224072022-03-26T18:54:02ZOxygen-regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase A genes: similarities with the erythropoietin 3' enhancer.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:69e70f53-caeb-4478-9c78-e3ba68722407EnglishSymplectic Elements at Oxford1994Firth, JEbert, BPugh, CRatcliffe, PProduction of the glycoprotein hormone erythropoietin (Epo) in response to hypoxic stimuli is almost entirely restricted to particular cells within liver and kidney, yet the transcriptional enhancer lying 3' to the Epo gene shows activity inducible by hypoxia after transfection into a wide variety of cultured cells. The implication of this finding is that many cells which do not produce Epo contain a similar, if not identical, oxygen-regulated control system, suggesting that the same system is involved in the regulation of other genes. We report that the human phosphoglycerate kinase 1 and mouse lactate dehydrogenase A genes are induced by hypoxia with characteristics which resemble induction of the Epo gene. In each case expression is induced by cobalt, but not by cyanide, and hypoxic induction is blocked by the protein-synthesis inhibitor cycloheximide. We show that the relevant cis-acting control sequences are located in the 5' flanking regions of the two genes, and we define an 18-bp element in the 5' flanking sequence of the phosphoglycerate kinase 1 gene which is both necessary and sufficient for the hypoxic response, and which has sequence and protein-binding similarities to the hypoxia-inducible factor 1 binding site within the Epo 3' enhancer. |
| spellingShingle | Firth, J Ebert, B Pugh, C Ratcliffe, P Oxygen-regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase A genes: similarities with the erythropoietin 3' enhancer. |
| title | Oxygen-regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase A genes: similarities with the erythropoietin 3' enhancer. |
| title_full | Oxygen-regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase A genes: similarities with the erythropoietin 3' enhancer. |
| title_fullStr | Oxygen-regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase A genes: similarities with the erythropoietin 3' enhancer. |
| title_full_unstemmed | Oxygen-regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase A genes: similarities with the erythropoietin 3' enhancer. |
| title_short | Oxygen-regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase A genes: similarities with the erythropoietin 3' enhancer. |
| title_sort | oxygen regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase a genes similarities with the erythropoietin 3 enhancer |
| work_keys_str_mv | AT firthj oxygenregulatedcontrolelementsinthephosphoglyceratekinase1andlactatedehydrogenaseagenessimilaritieswiththeerythropoietin3enhancer AT ebertb oxygenregulatedcontrolelementsinthephosphoglyceratekinase1andlactatedehydrogenaseagenessimilaritieswiththeerythropoietin3enhancer AT pughc oxygenregulatedcontrolelementsinthephosphoglyceratekinase1andlactatedehydrogenaseagenessimilaritieswiththeerythropoietin3enhancer AT ratcliffep oxygenregulatedcontrolelementsinthephosphoglyceratekinase1andlactatedehydrogenaseagenessimilaritieswiththeerythropoietin3enhancer |