A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals.
نویسندگان
چکیده
Understanding the principles governing mammalian gene regulation has been hampered by the difficulty in measuring in vivo binding dynamics of large numbers of transcription factors (TF) to DNA. Here, we develop a high-throughput Chromatin ImmunoPrecipitation (HT-ChIP) method to systematically map protein-DNA interactions. HT-ChIP was applied to define the dynamics of DNA binding by 25 TFs and 4 chromatin marks at 4 time-points following pathogen stimulus of dendritic cells. Analyzing over 180,000 TF-DNA interactions we find that TFs vary substantially in their temporal binding landscapes. This data suggests a model for transcription regulation whereby TF networks are hierarchically organized into cell differentiation factors, factors that bind targets prior to stimulus to prime them for induction, and factors that regulate specific gene programs. Overlaying HT-ChIP data on gene-expression dynamics shows that many TF-DNA interactions are established prior to the stimuli, predominantly at immediate-early genes, and identified specific TF ensembles that coordinately regulate gene-induction.
منابع مشابه
P-204: Evaluation of FMR1 Gene Regulatory Region for The Epigenetic Mark of H3K9 Acetylation in Blood Cells of Patients with Diminished Ovarian Reserve Reffered to Royan Institute
Background: Diminished ovarian reserve (DOR) is a heterogeneous disorder causing infertility, characterized by a decreased number of oocytes and high FSH level, the genetic cause of which is still unknown. The association between FMR1 premutations(50-200 CGG repeats) and the premature ovarian failure( POF) disease has suggested that FMR1 gene acts as a risk factor for POF and recently for DOR p...
متن کاملA Quantitative Model of Transcriptional Regulation Reveals the Influence of Binding Location on Expression
Understanding the mechanistic basis of transcriptional regulation has been a central focus of molecular biology since its inception. New high-throughput chromatin immunoprecipitation experiments have revealed that most regulatory proteins bind thousands of sites in mammalian genomes. However, the functional significance of these binding sites remains unclear. We present a quantitative model of ...
متن کاملRoles of Chromatin insulators in gene regulation and diseases
With advances in genetic science, the dynamic structure of eukaryotic genome is considered as basis of gene expression regulation. Long-distance communication between regulatory elements and target promoters is critical and the mechanisms responsible for this connection are just starting to emerge. Chromatin insulators are key determinants of proper gene regulation and precise organization of c...
متن کاملRecovering Genetic Regulatory Networks from Chromatin Immunoprecipitation and Steady-State Microarray Data
Recent advances in high-throughput DNA microarrays and chromatin immunoprecipitation (ChIP) assays have enabled the learning of the structure and functionality of genetic regulatory networks. In light of these heterogeneous data sets, this paper proposes a novel approach for reconstruction of genetic regulatory networks based on the posterior probabilities of gene regulations. Built within the ...
متن کاملMicroprocessor, Setx, Xrn2, and Rrp6 Co-operate to Induce Premature Termination of Transcription by RNAPII
Transcription elongation is increasingly recognized as an important mechanism of gene regulation. Here, we show that microprocessor controls gene expression in an RNAi-independent manner. Microprocessor orchestrates the recruitment of termination factors Setx and Xrn2, and the 3'-5' exoribonuclease, Rrp6, to initiate RNAPII pausing and premature termination at the HIV-1 promoter through cleavag...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Molecular cell
دوره 47 5 شماره
صفحات -
تاریخ انتشار 2012