RT Journal
A1 Hoffman, Brad G.
A1 Robertson, Gordon
A1 Zavaglia, Bogard
A1 Beach, Mike
A1 Cullum, Rebecca
A1 Lee, Sam
A1 Soukhatcheva, Galina
A1 Li, Leping
A1 Wederell, Elizabeth D.
A1 Thiessen, Nina
A1 Bilenky, Mikhail
A1 Cezard, Timothee
A1 Tam, Angela
A1 Kamoh, Baljit
A1 Birol, Inanc
A1 Dai, Derek
A1 Zhao, YongJun
A1 Hirst, Martin
A1 Verchere, C. Bruce
A1 Helgason, Cheryl D.
A1 Marra, Marco A.
A1 Jones, Steven J.M.
A1 Hoodless, Pamela A.
T1 Locus co-occupancy, nucleosome positioning, and H3K4me1 regulate the functionality of FOXA2-, HNF4A-, and PDX1-bound loci in islets and liver
JF Genome Research 
JO Genome Research 
YR 2010 
FD August 01 
VO 20 
IS 8 
SP 1037 
OP 1051 
DO 10.1101/gr.104356.109 
UL http://genome.cshlp.org/content/20/8/1037.abstract 
AB The liver and pancreas share a common origin and coexpress several transcription factors. To gain insight into the transcriptional networks regulating the function of these tissues, we globally identify binding sites for FOXA2 in adult mouse islets and liver, PDX1 in islets, and HNF4A in liver. Because most eukaryotic transcription factors bind thousands of loci, many of which are thought to be inactive, methods that can discriminate functionally active binding events are essential for the interpretation of genome-wide transcription factor binding data. To develop such a method, we also generated genome-wide H3K4me1 and H3K4me3 localization data in these tissues. By analyzing our binding and histone methylation data in combination with comprehensive gene expression data, we show that H3K4me1 enrichment profiles discriminate transcription factor occupied loci into three classes: those that are functionally active, those that are poised for activation, and those that reflect pioneer-like transcription factor activity. Furthermore, we demonstrate that the regulated presence of H3K4me1-marked nucleosomes at transcription factor occupied promoters and enhancers controls their activity, implicating both tissue-specific transcription factor binding and nucleosome remodeling complex recruitment in determining tissue-specific gene expression. Finally, we apply these approaches to generate novel insights into how FOXA2, PDX1, and HNF4A cooperate to drive islet- and liver-specific gene expression.