TY  - JOUR
A1  - Zhu, Cong
A1  - Byers, Kelsey J.R.P.
A1  - McCord, Rachel Patton
A1  - Shi, Zhenwei
A1  - Berger, Michael F.
A1  - Newburger, Daniel E.
A1  - Saulrieta, Katrina
A1  - Smith, Zachary
A1  - Shah, Mita V.
A1  - Radhakrishnan, Mathangi
A1  - Philippakis, Anthony A.
A1  - Hu, Yanhui
A1  - De Masi, Federico
A1  - Pacek, Marcin
A1  - Rolfs, Andreas
A1  - Murthy, Tal
A1  - LaBaer, Joshua
A1  - Bulyk, Martha L.
T1  - High-resolution DNA-binding specificity analysis of yeast transcription factors
Y1  - 2009/04/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 556 
EP  - 566 
DO  - 10.1101/gr.090233.108 
VL  - 19 
IS  - 4 
UR  - http://genome.cshlp.org/content/19/4/556.abstract 
N2  - Transcription factors (TFs) regulate the expression of genes through sequence-specific interactions with DNA-binding sites. However, despite recent progress in identifying in vivo TF binding sites by microarray readout of chromatin immunoprecipitation (ChIP-chip), nearly half of all known yeast TFs are of unknown DNA-binding specificities, and many additional predicted TFs remain uncharacterized. To address these gaps in our knowledge of yeast TFs and their cis regulatory sequences, we have determined high-resolution binding profiles for 89 known and predicted yeast TFs, over more than 2.3 million gapped and ungapped 8-bp sequences (“k-mers”). We report 50 new or significantly different direct DNA-binding site motifs for yeast DNA-binding proteins and motifs for eight proteins for which only a consensus sequence was previously known; in total, this corresponds to over a 50% increase in the number of yeast DNA-binding proteins with experimentally determined DNA-binding specificities. Among other novel regulators, we discovered proteins that bind the PAC (Polymerase A and C) motif (GATGAG) and regulate ribosomal RNA (rRNA) transcription and processing, core cellular processes that are constituent to ribosome biogenesis. In contrast to earlier data types, these comprehensive k-mer binding data permit us to consider the regulatory potential of genomic sequence at the individual word level. These k-mer data allowed us to reannotate in vivo TF binding targets as direct or indirect and to examine TFs' potential effects on gene expression in ∼1700 environmental and cellular conditions. These approaches could be adapted to identify TFs and cis regulatory elements in higher eukaryotes. 
ER  -