CHD1 regulates cell fate determination by activation of differentiation-induced genes

Simon J Baumgart, Zeynab Najafova, Tareq Hossan, Wanhua Xie, Sankari Nagarajan, Vijayalakshmi Kari, Nicholas Ditzel, Moustapha Kassem, Steven A Johnsen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

158 Downloads (Pure)

Resumé

The coordinated temporal and spatial activation of gene expression is essential for proper stem cell differentiation. The Chromodomain Helicase DNA-binding protein 1 (CHD1) is a chromatin remodeler closely associated with transcription and nucleosome turnover downstream of the transcriptional start site (TSS). In this study, we show that CHD1 is required for the induction of osteoblast-specific gene expression, extracellular-matrix mineralization and ectopic bone formation in vivo. Genome-wide occupancy analyses revealed increased CHD1 occupancy around the TSS of differentiation-activated genes. Furthermore, we observed that CHD1-dependent genes are mainly induced during osteoblast differentiation and are characterized by higher levels of CHD1 occupancy around the TSS. Interestingly, CHD1 depletion resulted in increased pausing of RNA Polymerase II (RNAPII) and decreased H2A.Z occupancy close to the TSS, but not at enhancer regions. These findings reveal a novel role for CHD1 during osteoblast differentiation and provide further insights into the intricacies of epigenetic regulatory mechanisms controlling cell fate determination.

OriginalsprogEngelsk
TidsskriftNucleic Acids Research
Vol/bind45
Udgave nummer13
Sider (fra-til)7722-7735
ISSN0305-1048
DOI
StatusUdgivet - 2017

Fingeraftryk

DNA-Binding Proteins
Osteoblasts
Nucleosomes
RNA Polymerase II
Osteogenesis
Epigenomics
Cell Differentiation

Citer dette

Baumgart, S. J., Najafova, Z., Hossan, T., Xie, W., Nagarajan, S., Kari, V., ... Johnsen, S. A. (2017). CHD1 regulates cell fate determination by activation of differentiation-induced genes. Nucleic Acids Research, 45(13), 7722-7735. https://doi.org/10.1093/nar/gkx377
Baumgart, Simon J ; Najafova, Zeynab ; Hossan, Tareq ; Xie, Wanhua ; Nagarajan, Sankari ; Kari, Vijayalakshmi ; Ditzel, Nicholas ; Kassem, Moustapha ; Johnsen, Steven A. / CHD1 regulates cell fate determination by activation of differentiation-induced genes. I: Nucleic Acids Research. 2017 ; Bind 45, Nr. 13. s. 7722-7735.
@article{72ac298d5b65461c925639e95804a560,
title = "CHD1 regulates cell fate determination by activation of differentiation-induced genes",
abstract = "The coordinated temporal and spatial activation of gene expression is essential for proper stem cell differentiation. The Chromodomain Helicase DNA-binding protein 1 (CHD1) is a chromatin remodeler closely associated with transcription and nucleosome turnover downstream of the transcriptional start site (TSS). In this study, we show that CHD1 is required for the induction of osteoblast-specific gene expression, extracellular-matrix mineralization and ectopic bone formation in vivo. Genome-wide occupancy analyses revealed increased CHD1 occupancy around the TSS of differentiation-activated genes. Furthermore, we observed that CHD1-dependent genes are mainly induced during osteoblast differentiation and are characterized by higher levels of CHD1 occupancy around the TSS. Interestingly, CHD1 depletion resulted in increased pausing of RNA Polymerase II (RNAPII) and decreased H2A.Z occupancy close to the TSS, but not at enhancer regions. These findings reveal a novel role for CHD1 during osteoblast differentiation and provide further insights into the intricacies of epigenetic regulatory mechanisms controlling cell fate determination.",
keywords = "Journal Article",
author = "Baumgart, {Simon J} and Zeynab Najafova and Tareq Hossan and Wanhua Xie and Sankari Nagarajan and Vijayalakshmi Kari and Nicholas Ditzel and Moustapha Kassem and Johnsen, {Steven A}",
note = "{\circledC} The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.",
year = "2017",
doi = "10.1093/nar/gkx377",
language = "English",
volume = "45",
pages = "7722--7735",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Heinemann",
number = "13",

}

Baumgart, SJ, Najafova, Z, Hossan, T, Xie, W, Nagarajan, S, Kari, V, Ditzel, N, Kassem, M & Johnsen, SA 2017, 'CHD1 regulates cell fate determination by activation of differentiation-induced genes', Nucleic Acids Research, bind 45, nr. 13, s. 7722-7735. https://doi.org/10.1093/nar/gkx377

CHD1 regulates cell fate determination by activation of differentiation-induced genes. / Baumgart, Simon J; Najafova, Zeynab; Hossan, Tareq; Xie, Wanhua; Nagarajan, Sankari; Kari, Vijayalakshmi; Ditzel, Nicholas; Kassem, Moustapha; Johnsen, Steven A.

I: Nucleic Acids Research, Bind 45, Nr. 13, 2017, s. 7722-7735.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - CHD1 regulates cell fate determination by activation of differentiation-induced genes

AU - Baumgart, Simon J

AU - Najafova, Zeynab

AU - Hossan, Tareq

AU - Xie, Wanhua

AU - Nagarajan, Sankari

AU - Kari, Vijayalakshmi

AU - Ditzel, Nicholas

AU - Kassem, Moustapha

AU - Johnsen, Steven A

N1 - © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2017

Y1 - 2017

N2 - The coordinated temporal and spatial activation of gene expression is essential for proper stem cell differentiation. The Chromodomain Helicase DNA-binding protein 1 (CHD1) is a chromatin remodeler closely associated with transcription and nucleosome turnover downstream of the transcriptional start site (TSS). In this study, we show that CHD1 is required for the induction of osteoblast-specific gene expression, extracellular-matrix mineralization and ectopic bone formation in vivo. Genome-wide occupancy analyses revealed increased CHD1 occupancy around the TSS of differentiation-activated genes. Furthermore, we observed that CHD1-dependent genes are mainly induced during osteoblast differentiation and are characterized by higher levels of CHD1 occupancy around the TSS. Interestingly, CHD1 depletion resulted in increased pausing of RNA Polymerase II (RNAPII) and decreased H2A.Z occupancy close to the TSS, but not at enhancer regions. These findings reveal a novel role for CHD1 during osteoblast differentiation and provide further insights into the intricacies of epigenetic regulatory mechanisms controlling cell fate determination.

AB - The coordinated temporal and spatial activation of gene expression is essential for proper stem cell differentiation. The Chromodomain Helicase DNA-binding protein 1 (CHD1) is a chromatin remodeler closely associated with transcription and nucleosome turnover downstream of the transcriptional start site (TSS). In this study, we show that CHD1 is required for the induction of osteoblast-specific gene expression, extracellular-matrix mineralization and ectopic bone formation in vivo. Genome-wide occupancy analyses revealed increased CHD1 occupancy around the TSS of differentiation-activated genes. Furthermore, we observed that CHD1-dependent genes are mainly induced during osteoblast differentiation and are characterized by higher levels of CHD1 occupancy around the TSS. Interestingly, CHD1 depletion resulted in increased pausing of RNA Polymerase II (RNAPII) and decreased H2A.Z occupancy close to the TSS, but not at enhancer regions. These findings reveal a novel role for CHD1 during osteoblast differentiation and provide further insights into the intricacies of epigenetic regulatory mechanisms controlling cell fate determination.

KW - Journal Article

U2 - 10.1093/nar/gkx377

DO - 10.1093/nar/gkx377

M3 - Journal article

C2 - 28475736

VL - 45

SP - 7722

EP - 7735

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 13

ER -

Baumgart SJ, Najafova Z, Hossan T, Xie W, Nagarajan S, Kari V et al. CHD1 regulates cell fate determination by activation of differentiation-induced genes. Nucleic Acids Research. 2017;45(13):7722-7735. https://doi.org/10.1093/nar/gkx377