Core transcriptional regulatory circuitry in human hepatocytes.
We mapped the transcriptional regulatory circuitry for six master regulators in human hepatocytes using chromatin immunoprecipitation and high-resolution promoter microarrays. The results show that these regulators form a highly interconnected core circuitry, and reveal the local regulatory network motifs created by regulator-gene interactions. Autoregulation was a prominent theme among these regulators. We found that hepatocyte master regulators tend to bind promoter regions combinatorially and that the number of transcription factors bound to a promoter corresponds with observed gene expression. Our studies reveal portions of the core circuitry of human hepatocytes.
Odom
Duncan T
DT
Young Laboratory, Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Dowell
Robin D
RD
Jacobsen
Elizabeth S
ES
Nekludova
Lena
L
Rolfe
P Alexander
PA
Danford
Timothy W
TW
Gifford
David K
DK
Fraenkel
Ernest
E
Bell
Graeme I
GI
Young
Richard A
RA
D005786:Gene Expression Regulation; D022781:Hepatocytes; D006706:Homeostasis; D006801:Humans; D011401:Promoter Regions, Genetic; D040081:Protein Array Analysis; D014157:Transcription Factors; D014158:Transcription, Genetic
D014157:Transcription Factors