Chromodomain Helicase DNA-Binding Proteins in Stem Cells and Human Developmental Diseases

Micucci, Joseph A.; Sperry, Ethan D.; Martin, Donna M.

doi:10.1089/scd.2014.0544

Cited by 42 publications

(48 citation statements)

References 105 publications

(122 reference statements)

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“…Most CHDs are expressed in neurons (Micucci et al., 2015); however, mass spectrometry analysis indicated that only CHD3, CHD4, and CHD5 are associated with NuRD in the embryonic cortex (Figures 1 and S1). Knockdown of CHD5 in the developing cortex induces severe defects of neural radial migration (Egan et al., 2013).…”

Section: Discussionmentioning

confidence: 99%

A Functional Switch of NuRD Chromatin Remodeling Complex Subunits Regulates Mouse Cortical Development

et al. 2016

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SummaryHistone modifications and chromatin remodeling represent universal mechanisms by which cells adapt their transcriptional response to rapidly changing environmental conditions. Extensive chromatin remodeling takes place during neuronal development, allowing the transition of pluripotent cells into differentiated neurons. Here, we report that the NuRD complex, which couples ATP-dependent chromatin remodeling with histone deacetylase activity, regulates mouse brain development. Subunit exchange of CHDs, the core ATPase subunits of the NuRD complex, is required for distinct aspects of cortical development. Whereas CHD4 promotes the early proliferation of progenitors, CHD5 facilitates neuronal migration and CHD3 ensures proper layer specification. Inhibition of each CHD leads to defects of neuronal differentiation and migration, which cannot be rescued by expressing heterologous CHDs. Finally, we demonstrate that NuRD complexes containing specific CHDs are recruited to regulatory elements and modulate the expression of genes essential for brain development.

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Section: Discussionmentioning

confidence: 99%

A Functional Switch of NuRD Chromatin Remodeling Complex Subunits Regulates Mouse Cortical Development

et al. 2016

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“…Deletion of CHD1 ATPase in yeast affected genome‐wide nucleosome organization in the coding regions of highly transcribed genes, suggesting a link to transcriptional elongation (Gkikopoulos et al ., ). CHD1 acts together with histone chaperones and plays a distinct role in post‐replication chromatin assembly and nucleosome spacing (Torigoe et al ., ; Li et al ., ; Micucci et al ., ).…”

Section: The Swr1/ino80 Iswi Lsh/rad54 and Chd1 Chromatin Remodelermentioning

confidence: 97%

Roles and activities of chromatin remodeling ATPases in plants

et al. 2015

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These authors contributed equally to this paper. SUMMARYChromatin remodeling ATPases and their associated complexes can alter the accessibility of the genome in the context of chromatin by using energy derived from the hydrolysis of ATP to change the positioning, occupancy and composition of nucleosomes. In animals and plants, these remodelers have been implicated in diverse processes ranging from stem cell maintenance and differentiation to developmental phase transitions and stress responses. Detailed investigation of their roles in individual processes has suggested a higher level of selectivity of chromatin remodeling ATPase activity than previously anticipated, and diverse mechanisms have been uncovered that can contribute to the selectivity. This review summarizes recent advances in understanding the roles and activities of chromatin remodeling ATPases in plants.

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“…CHD9 is an understudied member of the CHD family of chromatin remodellers [11,14,15,20], but has been suggested to remodel and bind to the promoters of osteogenic genes in mesenchymal stem cells and osteoprogenitors [17][18][19][20][21]. However, the precise biological roles CHD9 play remain relatively unknown, including whether it directly promotes transcription of its osteogenic gene targets.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, modification of traits is likely driven by small incremental changes to the expression and regulation of this suite of genes [3]. The relationships between gene expression and cis-regulation may be controlled through alterations to epigenetic modifiers (chromatin remodellers), proteins which drive broad changes in gene expression within a specific tissue or cell type [11]. One such mechanism to drive concerted changes in gene expression is through genome-wide alterations in chromatin organization [12,13].…”

Section: Introductionmentioning

confidence: 99%

“…CHD (chromodomain helicase DNA-binding) proteins are chromatin remodelling enzymes which reshape the local chromatin architecture to allow access to transcriptional machinery in a tissue-specific context [11,14]. CHD proteins facilitate various stages of gene expression, including binding and recruiting transcription factors, histone modifications, and transcriptional elongation, termination and processing [15].…”

Section: Introductionmentioning

confidence: 99%

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CHD9 upregulates RUNX2 and has a potential role in skeletal evolution

Newton

Pask

2020

BMC Mol and Cell Biol

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Background: Changes in gene regulation are widely recognized as an important driver of adaptive phenotypic evolution. However, the specific molecular mechanisms that underpin such changes are still poorly understood. Chromatin state plays an essential role in gene regulation, by influencing the accessibility of coding loci to the transcriptional machinery. Changes in the function of chromatin remodellers are therefore strong candidates to drive changes in gene expression associated with phenotypic adaptation. Here, we identify amino acid homoplasies in the chromatin remodeller CHD9, shared between the extinct marsupial thylacine and eutherian wolf which show remarkable skull convergence. CHD9 is involved in osteogenesis, though its role in the process is still poorly understood. We examine whether CHD9 is able to regulate the expression of osteogenic target genes and examine the function of a key substitution in the CHD9 DNA binding domain.Results: We examined whether CHD9 was able to upregulate its osteogenic target genes, RUNX2, Osteocalcin (OC) and ALP in HEK293T cells. We found that overexpression of CHD9 upregulated RUNX2, the master regulator of osteoblast cell fate, but not the downstream genes OC or ALP, supporting the idea that CHD9 regulates osteogenic progenitors rather than terminal osteoblasts. We also found that the evolutionary substitution in the CHD9 DNA binding domain does not alter protein secondary structure, but was able to drive a small but insignificant increase in RUNX2 activation. Finally, CHD9 was unable to activate an episomal RUNX2 promoter-reporter construct, suggesting that CHD9 requires the full chromatin complement for its function. Conclusions: We provide new evidence to the role of CHD9 in osteogenic differentiation through its newly observed ability to upregulate the expression of RUNX2. Though we were unable to identify significant functional consequences of the evolutionary substitution in HEK293T cells, our study provides important steps forward in the functional investigation of protein homoplasy and its role in developmental processes. Mutations in coding genes may be a mechanism for driving adaptive changes in gene expression, and their validation is essential towards determining the functional consequences of evolutionary homoplasy.

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Chromodomain Helicase DNA-Binding Proteins in Stem Cells and Human Developmental Diseases

Cited by 42 publications

References 105 publications

A Functional Switch of NuRD Chromatin Remodeling Complex Subunits Regulates Mouse Cortical Development

A Functional Switch of NuRD Chromatin Remodeling Complex Subunits Regulates Mouse Cortical Development

Roles and activities of chromatin remodeling ATPases in plants

CHD9 upregulates RUNX2 and has a potential role in skeletal evolution

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