First name
Alessia
Last name
Curina
Year of Study
Research Center
Thesis Title
Dissection of the mechanisms controlling high constitutive activity of housekeeping and tissue-specific cis-regulatory elements
Thesis Abstract
The genetic information is identical within the organism but the mechanisms by
which different cell types achieve specialized functions interpreting the same set of
instructions is not completely understood. It is now increasingly accepted that the
combination of different genomic elements, both promoters and enhancers, favors the
recruitment of different TFs, which in turn promotes the assembly of different preinitiation
complexes, guaranteeing heterogeneity in transcriptional outputs across
different tissues. Nevertheless, the cis-regulatory elements and the transcriptional
rules that control and maintain the expression of constitutively active genes are still
poorly characterized. Specifically, whether the constitutive activity of promoters and
enhancers relies on entirely distinct or instead shared regulators is unknown. By
dissecting the cis-regulatory repertoire of macrophages, we found that the ELF
subfamily of ETS proteins selectively bound within 60 bp from the transcription start
sites of highly active housekeeping genes. ELFs also bound constitutively active, but
not poised macrophage-specific enhancers and promoters. The role of ELFs in
promoting constitutive transcription is suggested by multiple evidences: ELF sites
enabled transcriptional activation by endogenous and minimal synthetic promoters;
ELF recruitment was stabilized by the transcriptional machinery, and ELF proteins
mediated recruitment of transcriptional and chromatin regulators to core promoters.
These data indicate that a distinct subfamily of ETS proteins imparts high
transcriptional activity to a broad range of housekeeping and tissue-specific cisregulatory
elements, which is consistent with the role of an ETS family ancestor in
core promoter regulation in a lower eukaryote.
which different cell types achieve specialized functions interpreting the same set of
instructions is not completely understood. It is now increasingly accepted that the
combination of different genomic elements, both promoters and enhancers, favors the
recruitment of different TFs, which in turn promotes the assembly of different preinitiation
complexes, guaranteeing heterogeneity in transcriptional outputs across
different tissues. Nevertheless, the cis-regulatory elements and the transcriptional
rules that control and maintain the expression of constitutively active genes are still
poorly characterized. Specifically, whether the constitutive activity of promoters and
enhancers relies on entirely distinct or instead shared regulators is unknown. By
dissecting the cis-regulatory repertoire of macrophages, we found that the ELF
subfamily of ETS proteins selectively bound within 60 bp from the transcription start
sites of highly active housekeeping genes. ELFs also bound constitutively active, but
not poised macrophage-specific enhancers and promoters. The role of ELFs in
promoting constitutive transcription is suggested by multiple evidences: ELF sites
enabled transcriptional activation by endogenous and minimal synthetic promoters;
ELF recruitment was stabilized by the transcriptional machinery, and ELF proteins
mediated recruitment of transcriptional and chromatin regulators to core promoters.
These data indicate that a distinct subfamily of ETS proteins imparts high
transcriptional activity to a broad range of housekeeping and tissue-specific cisregulatory
elements, which is consistent with the role of an ETS family ancestor in
core promoter regulation in a lower eukaryote.
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