CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression

Chris M Egan; Ulrika Nyman; Julie Skotte; Gundula Streubel; Siobhán Turner; David J O'Connell; Vilma Rraklli; Michael J Dolan; Naomi Chadderton; Klaus Hansen; Gwyneth Jane Farrar; Kristian Helin; Johan Holmberg; Adrian P Bracken

doi:10.1016/j.devcel.2013.07.008

CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression

Chris M Egan, Ulrika Nyman, Julie Skotte, Gundula Streubel, Siobhán Turner, David J O'Connell, Vilma Rraklli, Michael J Dolan, Naomi Chadderton, Klaus Hansen, Gwyneth Jane Farrar, Kristian Helin, Johan Holmberg, Adrian P Bracken

The Danish Stem Cell Center

67 Citations (Scopus)

Abstract

The chromatin remodeler CHD5 is expressed in neural tissue and is frequently deleted in aggressive neuroblastoma. Very little is known about the function of CHD5 in the nervous system or its mechanism of action. Here we report that depletion of Chd5 in the developing neocortex blocks neuronal differentiation and leads to an accumulation of undifferentiated progenitors. CHD5 binds a large cohort of genes and is required for facilitating the activation of neuronal genes. It also binds a cohort of Polycomb targets and is required for the maintenance of H3K27me3 on these genes. Interestingly, the chromodomains of CHD5 directly bind H3K27me3 and are required for neuronal differentiation. In the absence of CHD5, a subgroup of Polycomb-repressed genes becomes aberrantly expressed. These findings provide insights into the regulatory role of CHD5 during neurogenesis and suggest how inactivation of this candidate tumor suppressor might contribute to neuroblastoma.

Original language	English
Journal	Developmental Cell
Volume	26
Issue number	3
Pages (from-to)	223-36
Number of pages	14
ISSN	1534-5807
DOIs	https://doi.org/10.1016/j.devcel.2013.07.008
Publication status	Published - 12 Aug 2013

Keywords

Animals
Cell Differentiation
Cell Line, Tumor
Cerebral Cortex
DNA Helicases
Embryonic Stem Cells
Female
Gene Expression Regulation, Developmental
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
HEK293 Cells
Humans
Mice
Mice, Inbred Strains
Nerve Tissue Proteins
Neuroblastoma
Neurogenesis
Neurons
Polycomb-Group Proteins
Pregnancy
Retina

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Egan, C. M., Nyman, U., Skotte, J., Streubel, G., Turner, S., O'Connell, D. J., Rraklli, V., Dolan, M. J., Chadderton, N., Hansen, K., Farrar, G. J., Helin, K., Holmberg, J., & Bracken, A. P. (2013). CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression. Developmental Cell, 26(3), 223-36. https://doi.org/10.1016/j.devcel.2013.07.008

Egan, CM, Nyman, U, Skotte, J, Streubel, G, Turner, S, O'Connell, DJ, Rraklli, V, Dolan, MJ, Chadderton, N, Hansen, K, Farrar, GJ, Helin, K, Holmberg, J & Bracken, AP 2013, 'CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression', Developmental Cell, vol. 26, no. 3, pp. 223-36. https://doi.org/10.1016/j.devcel.2013.07.008

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title = "CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression",

abstract = "The chromatin remodeler CHD5 is expressed in neural tissue and is frequently deleted in aggressive neuroblastoma. Very little is known about the function of CHD5 in the nervous system or its mechanism of action. Here we report that depletion of Chd5 in the developing neocortex blocks neuronal differentiation and leads to an accumulation of undifferentiated progenitors. CHD5 binds a large cohort of genes and is required for facilitating the activation of neuronal genes. It also binds a cohort of Polycomb targets and is required for the maintenance of H3K27me3 on these genes. Interestingly, the chromodomains of CHD5 directly bind H3K27me3 and are required for neuronal differentiation. In the absence of CHD5, a subgroup of Polycomb-repressed genes becomes aberrantly expressed. These findings provide insights into the regulatory role of CHD5 during neurogenesis and suggest how inactivation of this candidate tumor suppressor might contribute to neuroblastoma.",

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author = "Egan, {Chris M} and Ulrika Nyman and Julie Skotte and Gundula Streubel and Siobh{\'a}n Turner and O'Connell, {David J} and Vilma Rraklli and Dolan, {Michael J} and Naomi Chadderton and Klaus Hansen and Farrar, {Gwyneth Jane} and Kristian Helin and Johan Holmberg and Bracken, {Adrian P}",

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T1 - CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression

AU - Egan, Chris M

AU - Nyman, Ulrika

AU - Skotte, Julie

AU - Streubel, Gundula

AU - Turner, Siobhán

AU - O'Connell, David J

AU - Rraklli, Vilma

AU - Dolan, Michael J

AU - Chadderton, Naomi

AU - Hansen, Klaus

AU - Farrar, Gwyneth Jane

AU - Helin, Kristian

AU - Holmberg, Johan

AU - Bracken, Adrian P

PY - 2013/8/12

Y1 - 2013/8/12

N2 - The chromatin remodeler CHD5 is expressed in neural tissue and is frequently deleted in aggressive neuroblastoma. Very little is known about the function of CHD5 in the nervous system or its mechanism of action. Here we report that depletion of Chd5 in the developing neocortex blocks neuronal differentiation and leads to an accumulation of undifferentiated progenitors. CHD5 binds a large cohort of genes and is required for facilitating the activation of neuronal genes. It also binds a cohort of Polycomb targets and is required for the maintenance of H3K27me3 on these genes. Interestingly, the chromodomains of CHD5 directly bind H3K27me3 and are required for neuronal differentiation. In the absence of CHD5, a subgroup of Polycomb-repressed genes becomes aberrantly expressed. These findings provide insights into the regulatory role of CHD5 during neurogenesis and suggest how inactivation of this candidate tumor suppressor might contribute to neuroblastoma.

AB - The chromatin remodeler CHD5 is expressed in neural tissue and is frequently deleted in aggressive neuroblastoma. Very little is known about the function of CHD5 in the nervous system or its mechanism of action. Here we report that depletion of Chd5 in the developing neocortex blocks neuronal differentiation and leads to an accumulation of undifferentiated progenitors. CHD5 binds a large cohort of genes and is required for facilitating the activation of neuronal genes. It also binds a cohort of Polycomb targets and is required for the maintenance of H3K27me3 on these genes. Interestingly, the chromodomains of CHD5 directly bind H3K27me3 and are required for neuronal differentiation. In the absence of CHD5, a subgroup of Polycomb-repressed genes becomes aberrantly expressed. These findings provide insights into the regulatory role of CHD5 during neurogenesis and suggest how inactivation of this candidate tumor suppressor might contribute to neuroblastoma.

KW - Animals

KW - Cell Differentiation

KW - Cell Line, Tumor

KW - Cerebral Cortex

KW - DNA Helicases

KW - Embryonic Stem Cells

KW - Female

KW - Gene Expression Regulation, Developmental

KW - Gene Expression Regulation, Neoplastic

KW - Gene Knockdown Techniques

KW - HEK293 Cells

KW - Humans

KW - Mice

KW - Mice, Inbred Strains

KW - Nerve Tissue Proteins

KW - Neuroblastoma

KW - Neurogenesis

KW - Neurons

KW - Polycomb-Group Proteins

KW - Pregnancy

KW - Retina

U2 - 10.1016/j.devcel.2013.07.008

DO - 10.1016/j.devcel.2013.07.008

M3 - Journal article

C2 - 23948251

SN - 1534-5807

VL - 26

SP - 223

EP - 236

JO - Developmental Cell

JF - Developmental Cell

IS - 3

ER -

CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression

Abstract

Keywords

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