@article{daba836f62fe45d08d7f826beac8b9ff,
title = "Tissue-specific BMAL1 cistromes reveal that rhythmic transcription is associated with rhythmic enhancer–enhancer interactions",
abstract = "The mammalian circadian clock relies on the transcription factor CLOCK:BMAL1 to coordinate the rhythmic expression of thousands of genes. Consistent with the various biological functions under clock control, rhythmic gene expression is tissue-specific despite an identical clockwork mechanism in every cell. Here we show that BMAL1 DNA binding is largely tissue-specific, likely because of differences in chromatin accessibility between tissues and cobinding of tissue-specific transcription factors. Our results also indicate that BMAL1 ability to drive tissue-specific rhythmic transcription is associated with not only the activity of BMAL1-bound enhancers but also the activity of neighboring enhancers. Characterization of physical interactions between BMAL1 enhancers and other cis-regulatory regions by RNA polymerase II chromatin interaction analysis by paired-end tag (ChIA-PET) reveals that rhythmic BMAL1 target gene expression correlates with rhythmic chromatin interactions. These data thus support that much of BMAL1 target gene transcription depends on BMAL1 capacity to rhythmically regulate a network of enhancers.",
keywords = "Circadian clock, Enhancer, Enhancer interactions, Tissue-specific cistromes, Transcription",
author = "Beytebiere, {Joshua R.} and Trott, {Alexandra J.} and Greenwell, {Ben J.} and Osborne, {Collin A.} and Helene Vitet and Jessica Spence and Seung-Hee Yoo and Zheng Chen and Takahashi, {Joseph S.} and Noushin Ghaffari and Menet, {Jerome S.}",
note = "Funding Information: We thank Christopher Bradfield for kindly providing the Bmal1−/− mouse; Craig Kaplan, Christine Merlin, and Aldrin Lugena for insightful suggestions at various stages of the project; Christine Merlin, Deborah Bell-Pedersen, and Paul Hardin for comments on the manuscript; the Texas A&M Institute for Genome Sciences and Society for providing access and maintenance to their high-performance computing cluster; Michael Rosbash, Kate Abruzzi, and Ryanne Spann for helping with sequencing BMAL1 ChIP-seq libraries; and Charles Johnson and Richard Metz for helping with sequencing the ChIA-PET libraries. We are also grateful to Paul Hardin and Matthew Sachs laboratories for technical support. This work was supported by startup funds from Texas A&M University. The laboratory of S.-H.Y. is supported by the National Institute of General Medical Sciences (R01GM114424), and the laboratory of Z.C. is supported by the Robert A. Welch Foundation (AU-1731-20160319) and the National Institute on Aging (R01AG045828). J.S.T. is an Investigator in the Howard Hughes Medical Institute. Funding Information: We thank Christopher Bradfield for kindly providing the Bmal1−/− mouse; Craig Kaplan, Christine Merlin, and Aldrin Lugena for insightful suggestions at various stages of the project; Christine Merlin, Deborah Bell-Pedersen, and Paul Hardin for comments on the manuscript; the Texas A&M Institute for Genome Sciences and Society for providing access and maintenance to their high-performance computing cluster; Michael Rosbash, Kate Abruzzi, and Ryanne Spann for helping with sequencing BMAL1 ChIP-seq libraries; and Charles Johnson and Richard Metz for helping with sequencing the ChIA-PET libraries. We are also grateful to Paul Hardin and Matthew Sachs laboratories for technical support. This work was supported by startup funds from Texas A&M University. The laboratory of S.-H.Y. is supported by the National Institute of General Medical Sciences (R01GM114424), and the laboratory of Z.C. is supported by the Robert A. Welch Foundation (AU-1731-20160319) and the National Institute on Aging (R01AG045828). J.S.T. is an Investigator in the Howard Hughes Medical Institute. Author contributions: J.R.B. and J.S.M. conceived and designed the research. J.R.B. performed most of the experiments and the bioinformatics analysis. J.S.M. performed the ChIA-PET experiments with the help of A.J.T. and J.R.B. B.G., C.A.O., and J.S.M. helped with the bioinformatics analysis. J.S. and H.V. performed ChIPs at an early stage of the project. S.-H.Y., Z.C., and J.S.T. contributed to the BMAL1 antibody. N.G. helped with the ChIA-PET bioinformatics analysis. J.R.B. and J.S.M. wrote the manuscript. Publisher Copyright: {\textcopyright} 2019 Beytebiere et al.",
year = "2019",
month = mar,
day = "1",
doi = "10.1101/gad.322198.118",
language = "English (US)",
volume = "33",
pages = "294--309",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "5-6",
}