We show that HEM1 (encoding 5-aminolevulinate synthase) expression, while constitutive under all steady-state growth conditions tested, is activated by the HAP2-HAP3 global activation system that controls expression of apocytochromes. This finding creates a paradox because apocytochrome activation by HAP2-HAP3 is highly regulated, subject to induction by heme, and subject to further derepression by a shift from glucose medium to one containing a nonfermentable carbon source. We clarify this issue by showing that HEM1 is subject to two additional layers of control that mask regulatory changes. First is a second activation system acting at a site close to the HAP2-HAP3 target sequence that keeps HEM1 turned on under conditions of heme deficiency. Second is a regulated negative control site downstream of the upstream activation site that counteracts derepression in medium containing a nonfermentable carbon source. Thus, transcription of the constitutive gene is actually a composite of opposing regulatory sites. This complex regulatory arrangement may exist to allow HEM1 to be coordinated transiently with apocytochromes for transition to respiratory growth. Conversely, it may reflect the alteration of HEM1 from a regulated to a constitutive gene over evolution.

• PMID: 3321068
• DOI full text
• PMC full text
• PubMed
• PubTator

Reference Type

Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.S.

Authors

Keng T, Guarente L

Primary Lit For

Additional Lit For

Review For