Transcription Induction Integrated by Nuclear Receptor Coregulators

Studies carried out during the past decade have
shown that transcription of inducible
eukaryotic genes involves sequential chromatin
modifications by promoter-specific transcription
factors and a class of proteins called transcription
coregulators. First, this work identifed
important chromatin modifications and modifying
complexes at the CYP17 transcription start site and
nearby steroidogenic factor-1 (SF-1) binding site.
Post translational modifications (PTMs) to SF-1 also
occur as this transcription factor interacts with
the promoter. In addition, ACTH/cAMP signaling in
adrenal cortex alters SF-1-containing chromatin-
modifying complexes during the early phase of
transcriptional induction of CYP17. Chromatin
IP (ChIP) and mammalian two hybrid experiments
identified complexes which are cAMP-inducible, but
sensitive to the SF-1 antagonist sphingosine. SF-1
PTMs at the ligand binding pocket opening were found
to be required for CYP17 transcription. Last,
certain corepressors are protein kinase A
(PKA) targets and are functionally sensitive to PKA-
dependent NADH accumulation. Thus, signaling,
metabolism, and transcription are integrated.

Autorentext

Eric Dammer was raised in Bergen County, New Jersey. He studied at UC Santa Cruz and later finished undergraduate studies at Florida Gulf Coast University in Ft. Myers, Florida in 2003. He was an HHMI intern at Georgia Tech before entering the Biology PhD program 2003-2008. He is currently a postdoc at Emory University in Atlanta, GA.

Klappentext

Studies carried out during the past decade have shown that transcription of inducible eukaryotic genes involves sequential chromatin modifications by promoter-specific transcription factors and a class of proteins called transcription coregulators. First, this work identifed important chromatin modifications and modifying complexes at the CYP17 transcription start site and nearby steroidogenic factor-1 (SF-1) binding site. Post translational modifications (PTMs) to SF-1 also occur as this transcription factor interacts with the promoter. In addition, ACTH/cAMP signaling in adrenal cortex alters SF-1-containing chromatin-modifying complexes during the early phase of transcriptional induction of CYP17. Chromatin IP (ChIP) and mammalian two hybrid experiments identified complexes which are cAMP-inducible, but sensitive to the SF-1 antagonist sphingosine. SF-1 PTMs at the ligand binding pocket opening were found to be required for CYP17 transcription. Last, certain corepressors are protein kinase A (PKA) targets and are functionally sensitive to PKA-dependent NADH accumulation. Thus, signaling, metabolism, and transcription are integrated.