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Abstract:
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The regulation of gene expression at the right time , place , and degree is crucial for many cellular processes such as proliferation and development . In addition , in order to maintain cellular life , cells must rapidly and appropriately respond to various environmental stimuli . Sequence -specific transcription factors (TFs ) can recognize functional regulatory DNA elements in a sequence -specific manner so that they can regulate only a specific group of genes , a process which enables cells to cope with diverse internal and external stimuli . Human has approximately 1 ,400 sequence -specific TFs whose aberrant expression causes a wide range of detrimental consequences including developmental disorders , diseases , and cancers ; therefore , it is pivotal to identify the binding sites of each sequence -specific TF in order to unravel its roles in and mechanisms of gene regulation .
Even though some TFs have been intensively studied , the majority of TFs still remain to be studied , particularly the tasks of identifying their genome -wide target genes and deciphering their biological roles in specific cellular contexts . Many questions remain unanswered : how many sites on the human genome a sequence -specific TF can bind ; whether all TF -bound sites are functional ; how a TF achieves binding specificity onto its targets ; how and to what extent a TF is involved in gene regulation . Comprehensive identification of the binding sites of sequence -specific TFs and follow -up molecular studies including gene expression microarrays will provide close answers to these questions .
Chromatin Immunoprecipitation coupled with recently developed high -throughput sequencing (ChIP -seq ) allows us to perform genome -scale unbiased identification of the binding sites of sequence -specific TFs . Here , to gain insight into gene regulatory functions of TFs as well as their influences on gene expression , we conducted , in diverse cell lines , genome -wide identification of the binding sites of several sequence -specific TFs (CTCF , E2F4 , MYC , Pol II ) that are involved in a wide range of biological functions , including cell proliferation , development , apoptosis , genome stability , and DNA repair . Analysis of ChIP -seq data provided not only comprehensive binding profiles of those TF across the genome in diverse cell lines , but also revealed tissue -specific binding of CTCF , MYC , and Pol II as well as combinatorial usage among these three factors . Analyses also showed that some CTCF binding sites were inherited from parents to children and regulated in an individual -specific as well as allele -specific manner . Finally , genome -wide target identification of several TFs will broaden our understanding of the gene regulatory roles of these sequence -specific TFs . |