Rehimi, Rizwan, Nikolic, Milos ORCID: 0000-0003-0029-7601, Cruz-Molina, Sara, Tebartz, Christina, Frommolt, Peter ORCID: 0000-0002-1966-8014, Mahabir, Esther, Clement-Ziza, Mathieu ORCID: 0000-0003-2763-249X and Rada-Iglesias, Alvaro ORCID: 0000-0001-7137-1341 (2016). Epigenomics-Based Identification of Major Cell Identity Regulators within Heterogeneous Cell Populations. Cell Reports, 17 (11). S. 3062 - 3077. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

Cellular heterogeneity within embryonic and adult tissues is involved in multiple biological and pathological processes. Here, we present a simple epigenomic strategy that allows the functional dissection of cellular heterogeneity. By integrating H3K27me3 chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) data, we demonstrate that the presence of broad H3K27me3 domains at transcriptionally active genes reflects the heterogeneous expression of major cell identity regulators. Using dorsoventral patterning of the spinal neural tube as a model, the proposed approach successfully identifies the majority of previously known dorsoventral patterning transcription factors with high sensitivity and precision. Moreover, poorly characterized patterning regulators can be similarly predicted, as shown for ZNF488, which confers p1/p2 neural progenitor identity. Finally, we show that, as our strategy is based on universal chromatin features, it can be used to functionally dissect cellular heterogeneity within various organisms and tissues, thus illustrating its potential applicability to a broad range of biological and pathological contexts.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Rehimi, RizwanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nikolic, MilosUNSPECIFIEDorcid.org/0000-0003-0029-7601UNSPECIFIED
Cruz-Molina, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tebartz, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frommolt, PeterUNSPECIFIEDorcid.org/0000-0002-1966-8014UNSPECIFIED
Mahabir, EstherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clement-Ziza, MathieuUNSPECIFIEDorcid.org/0000-0003-2763-249XUNSPECIFIED
Rada-Iglesias, AlvaroUNSPECIFIEDorcid.org/0000-0001-7137-1341UNSPECIFIED
URN: urn:nbn:de:hbz:38-252572
DOI: 10.1016/j.celrep.2016.11.046
Journal or Publication Title: Cell Reports
Volume: 17
Number: 11
Page Range: S. 3062 - 3077
Date: 2016
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 2211-1247
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
KEY DEVELOPMENTAL GENES; TRANSCRIPTION FACTORS; BIVALENT CHROMATIN; NAIVE PLURIPOTENCY; PLATE DEVELOPMENT; NEURONAL FATE; NEURAL-TUBE; SPINAL-CORD; ROOF PLATE; EXPRESSIONMultiple languages
Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/25257

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