Core transcriptional regulatory circuitry in human hepatocytes

被引:144
作者
Odom, Duncan T.
Dowell, Robin D.
Jacobsen, Elizabeth S.
Nekludova, Lena
Rolfe, P. Alexander
Danford, Timothy W.
Gifford, David K.
Fraenkel, Ernest
Bell, Graeme I.
Young, Richard A.
机构
[1] Whitehead Inst Biomed Res, Young Lab, Cambridge, MA 02142 USA
[2] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA
[3] MIT, Biol Engn Div, Cambridge, MA 02139 USA
[4] MIT, Dept Biol, Cambridge, MA 02139 USA
[5] Univ Chicago, Dept Med, Chicago, IL 60637 USA
[6] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA
关键词
autoregulation; hepatocyte; transcriptional regulation; regulatory hierarchy; chromatin immunoprecipitation;
D O I
10.1038/msb4100059
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
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页数:5
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