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Dynamic Transformations of Genome-wide Epigenetic Marking and Transcriptional Control Establish T Cell Identity

Zhang, Jingli A. and Mortazavi, Ali and Williams, Brian A. and Wold, Barbara J. and Rothenberg, Ellen V. (2012) Dynamic Transformations of Genome-wide Epigenetic Marking and Transcriptional Control Establish T Cell Identity. Cell, 149 (2). pp. 467-482. ISSN 0092-8674. PMCID PMC3336965. https://resolver.caltech.edu/CaltechAUTHORS:20120511-113721604

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Abstract

T 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.cell.2012.01.056 DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3336965/PubMed CentralArticle
ORCID:
AuthorORCID
Mortazavi, Ali0000-0002-4259-6362
Wold, Barbara J.0000-0003-3235-8130
Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 2012 Elsevier Inc. Received 9 August 2011. Revised 29 November 2011. Accepted 26 January 2012. Available online 12 April 2012. Published: April 12, 2012. We thank Lorian Schaeffer and Vijaya Kumar for library preparation and sequencing, Henry Amrhein and Diane Trout for data curation, Igor Antoshechkin for sequencing facility management, Diana Perez, Josh Verceles, and Rochelle Diamond for cell sorting and advice, Tian Ling, Georgi Marinov, and Hao Yuan Kueh for statistical advice and programming, Rothenberg group members for sharing advice and unpublished data, and Robert Butler, Lorena Sandoval, and Scott Washburn for care of the mice. Support was from NIH grants R33HL089123, R01CA090233, R01CA090233-08S1, and RC2CA148278, the Beckman Institute, the Millard and Muriel Jacobs Genetics and Genomics Center, the L.A. Garfinkle Memorial Laboratory Fund, the Al Sherman Foundation, the Bren Professorship (B.J.W.), and the A.B. Ruddock Professorship (E.V.R.).
Group:Millard and Muriel Jacobs Genetics and Genomics Laboratory
Funders:
Funding AgencyGrant Number
NIHR33HL089123
NIHR01CA090233
NIHR01CA090233-08S1
NIHRC2CA148278
Caltech Beckman InstituteUNSPECIFIED
Millard and Muriel Jacobs Genetics and Genomics CenterUNSPECIFIED
L.A. Garfinkle Memorial Laboratory FundUNSPECIFIED
Al Sherman FoundationUNSPECIFIED
Bren ProfessorshipUNSPECIFIED
Albert Billings Ruddock ProfessorshipUNSPECIFIED
Issue or Number:2
PubMed Central ID:PMC3336965
Record Number:CaltechAUTHORS:20120511-113721604
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20120511-113721604
Official Citation:Jingli A. Zhang, Ali Mortazavi, Brian A. Williams, Barbara J. Wold, Ellen V. Rothenberg, Dynamic Transformations of Genome-wide Epigenetic Marking and Transcriptional Control Establish T Cell Identity, Cell, Volume 149, Issue 2, 13 April 2012, Pages 467-482, ISSN 0092-8674, 10.1016/j.cell.2012.01.056.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:31437
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:11 May 2012 19:43
Last Modified:29 Oct 2019 23:04

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