STRUCTURAL DATA OF PC4: BOTH COACTIVATOR AND REPRESSOR OF TRANSCRIPTION ACTIVITY
Sjors H.W. Scheres, Jeroen Brandsen, Jean M.H. van den Elsen, Jan Kroon, Piet Gros
Department of Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands
Keywords: PC4; transcription
regulation
Regulation of gene transcription is fundamental
for living cells. Human positive cofactor (PC4) has a stimulating
function in the activator dependent class II gene transcription.
Recently the structure of the C-terminal domain (residues 63-127)
has been solved by X-ray diffraction in our lab [1]. This
structure shows a new structural motif reminiscent of the single
stranded (ss)DNA-binding motif in human replication protein A.
The orientation of the binding grooves on the dimer suggests that
two ssDNA strands running in opposite directions can be bound to
the protein. This agrees with the biochemical findings that
heteroduplex DNA can be bound to the protein with high affinity
[2]. Recent biochemical studies have shown that in the absence of
transcription factor IIH (TFIIH) the activator function of PC4 is
lost and transcription is strongly repressed by PC4 [3]. In the
same study it has been shown that PC4 can be phosphorylated by
TFIIH and TFIID. Most likely, phosphorylation is to take place on
the serine-rich N-terminal domain of PC4. We present structural
data of PC4 in the context of its combined role of both
coactivator and repressor of transcription activity.