TY - JOUR
T1 - Systematic identification of gene family regulators in mouse and human embryonic stem cells
AU - Aaronson, Yair
AU - Livyatan, Ilana
AU - Gokhman, David
AU - Meshorer, Eran
N1 - Publisher Copyright:
© 2016 The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2016/5/19
Y1 - 2016/5/19
N2 - Pluripotent self-renewing embryonic stem cells (ESCs) have been the focus of a growing number of high-throughput experiments, revealing the genome-wide locations of hundreds of transcription factors and histone modifications. While most of these datasets were used in a specific context, all datasets combined offer a comprehensive view of chromatin characteristics and regulatory elements that govern cell states. Here, using hundreds of datasets in ESCs, we generated colocalization maps of chromatin proteins and modifications, and built a discovery pipeline for regulatory proteins of gene families. By comparing genome-wide binding data with over-expression and knockdown analysis of hundreds of genes, we discovered that the pluripotency-related factor NR5A2 separates mitochondrial from cytosolic ribosomal genes, regulating their expression. We further show that genes with a common chromatin profile are enriched for distinct Gene Ontology (GO) categories. Our approach can be generalized to reveal common regulators of any gene group; discover novel gene families, and identify common genomic elements based on shared chromatin features.
AB - Pluripotent self-renewing embryonic stem cells (ESCs) have been the focus of a growing number of high-throughput experiments, revealing the genome-wide locations of hundreds of transcription factors and histone modifications. While most of these datasets were used in a specific context, all datasets combined offer a comprehensive view of chromatin characteristics and regulatory elements that govern cell states. Here, using hundreds of datasets in ESCs, we generated colocalization maps of chromatin proteins and modifications, and built a discovery pipeline for regulatory proteins of gene families. By comparing genome-wide binding data with over-expression and knockdown analysis of hundreds of genes, we discovered that the pluripotency-related factor NR5A2 separates mitochondrial from cytosolic ribosomal genes, regulating their expression. We further show that genes with a common chromatin profile are enriched for distinct Gene Ontology (GO) categories. Our approach can be generalized to reveal common regulators of any gene group; discover novel gene families, and identify common genomic elements based on shared chromatin features.
UR - http://www.scopus.com/inward/record.url?scp=84969916106&partnerID=8YFLogxK
U2 - 10.1093/nar/gkw259
DO - 10.1093/nar/gkw259
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C2 - 27084933
AN - SCOPUS:84969916106
SN - 0305-1048
VL - 44
SP - 4080
EP - 4089
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 9
ER -