A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals.
Mol Cell
; 47(5): 810-22, 2012 Sep 14.
Article
en En
| MEDLINE
| ID: mdl-22940246
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células Dendríticas
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Regulación de la Expresión Génica
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Inmunoprecipitación de Cromatina
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Ensayos Analíticos de Alto Rendimiento
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2012
Tipo del documento:
Article