Dynamic Transformations of Genome-wide Epigenetic Marking and Transcriptional Control Establish T Cell Identity
| Autor: | Jingli A. Zhang, Brian A. Williams, Ali Mortazavi, Ellen V. Rothenberg, Barbara J. Wold |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Transcription
Genetic Cellular differentiation T-Lymphocytes Computational biology GATA3 Transcription Factor Biology General Biochemistry Genetics and Molecular Biology Article Epigenesis Genetic Mice Transcription (biology) Proto-Oncogene Proteins Transcriptional regulation Histone code Animals Epigenetics Regulatory Elements Transcriptional Promoter Regions Genetic Transcription factor Regulation of gene expression Genetics Receptors Notch Biochemistry Genetics and Molecular Biology(all) Cell Differentiation Histone Code Mice Inbred C57BL Gene Expression Regulation Trans-Activators Transcription Factor Gene Genome-Wide Association Study Signal Transduction |
| Popis: | SummaryT cell development comprises a stepwise process of commitment from a multipotent precursor. To define molecular mechanisms controlling this progression, we probed five stages spanning the commitment process using RNA-seq and ChIP-seq to track genome-wide shifts in transcription, cohorts of active transcription factor genes, histone modifications at diverse classes of cis-regulatory elements, and binding repertoire of GATA-3 and PU.1, transcription factors with complementary roles in T cell development. The results highlight potential promoter-distal cis-regulatory elements in play and reveal both activation sites and diverse mechanisms of repression that silence genes used in alternative lineages. Histone marking is dynamic and reversible, and though permissive marks anticipate, repressive marks often lag behind changes in transcription. In vivo binding of PU.1 and GATA-3 relative to epigenetic marking reveals distinctive factor-specific rules for recruitment of these crucial transcription factors to different subsets of their potential sites, dependent on dose and developmental context. |
| Databáze: | OpenAIRE |
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