Abstract
Mammalian housekeeping genes show significantly lower promoter sequence conservation, especially upstream of position -500 with respect to the transcription start site, than genes expressed in a subset of tissues.
Highlights
Understanding the constraints that operate in mammalian gene promoter sequences is of key importance to understand the evolution of gene regulatory networks
We provide evidence that, in mammals, the simple expression patterns exhibited by housekeeping genes - expressed in all or most tissues are often associated with limited promoter sequence conservation, while tissue expression restrictions are associated with increasingly high promoter conservation
We describe that genes with housekeeping expression contain more divergent promoters than genes with a more restricted tissue expression
Summary
Understanding the constraints that operate in mammalian gene promoter sequences is of key importance to understand the evolution of gene regulatory networks. The correct functioning of multicellular organisms depends on a complex orchestration of gene regulatory events, which ensure that genes are expressed at the right time, place and level. Much of this regulation occurs at the level of gene transcription, and is mediated by specific interactions between transcription factors and cis-regulatory DNA motifs. A commonly used approach to assess the existence of evolutionary constraints and identify regulatory motifs is the identification of conserved non-coding sequences across orthologues. This rationale is behind several described 'phylogenetic footprinting' methods to discover functional regulatory sequences [2,3,4]
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