MBD2 and Multiple Domains of CHD4 Are Required for Transcriptional Repression by Mi-2/NuRD Complexes

Ramírez, Julita; Dege, Carissa; Kutateladze, Tatiana G.; Hagman, James

doi:10.1128/mcb.00819-12

Cited by 57 publications

(79 citation statements)

References 57 publications

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“…Importantly, several protein complexes, including ORC and PRC2, were identified that appear to read simultaneous modification states on both histones and DNA, likely through distinct subunits. Indeed, the Mi-2/NuRD complex can sense methylated DNA through its MBD2 subunit and unmodified H3 N-terminal tails through its CHD4 [112] and CHD5 subunits [113], and the repressive function of the MBD2/CHD4-containing NuRD complex appears to be dependent on the coordinate function of these two interactions [188]. …”

Section: Coordinate Function Of Histone and Dna Modifications In Cmentioning

confidence: 99%

Interpreting the language of histone and DNA modifications

Rothbart

Strahl

2014

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

636

508

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A major mechanism regulating the accessibility and function of eukaryotic genomes are the covalent modifications to DNA and histone proteins that dependably package our genetic information inside the nucleus of every cell. Formally postulated over a decade ago, it is becoming increasingly clear that post-translational modifications (PTMs) on histones act singly and in combination to form a language or ‘code’ that is read by specialized proteins to facilitate downstream functions in chromatin. Underappreciated at the time was the level of complexity harbored both within histone PTMs and their combinations, as well as within the proteins that read and interpret the language. In addition to histone PTMs, newly-identified DNA modifications that can recruit specific effector proteins has raised further awareness that histone PTMs operate within a broader language of epigenetic modifications to orchestrate the dynamic functions associated with chromatin. Here, we highlight key recent advances in our understanding of the epigenetic language encompassing histone and DNA modifications and foreshadow challenges that lie ahead as we continue our quest to decipher the fundamental mechanisms of chromatin regulation.

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Section: Coordinate Function Of Histone and Dna Modifications In Cmentioning

confidence: 99%

Interpreting the language of histone and DNA modifications

Rothbart

Strahl

2014

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

636

508

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“…The second subfamily consists of CHD3 (Mi2 α ) and CHD4 (Mi2 β ), which have two PHD-zinc finger motifs and each forms a nucleosome remodelling and deacetylation (NuRD) complex. The third subfamily consists of CHD6–CHD9, which was originally identified based on structural homology to other known CHD members [29,31]. Of all the CHD family members, CHD5 is most homologous to CHD3 and CHD4.…”

Section: Introductionmentioning

confidence: 99%

The tumour suppressor CHD5 forms a NuRD-type chromatin remodelling complex

Kolla

Naraparaju

Zhuang

et al. 2015

Biochemical Journal

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Eukaryotic gene expression is developmentally regulated, in part by chromatin remodelling, and its dysregulation has been linked to cancer. CHD5 (chromodomain helicase DNA-binding protein 5) is a tumour suppressor gene (TSG) that maps to a region of consistent deletion on 1p36.31 in neuroblastomas (NBs) and other tumour types. CHD5 encodes a protein with chromatin remodelling, helicase and DNA-binding motifs that is preferentially expressed in neural and testicular tissues. CHD5 is highly homologous to CHD3 and CHD4, which are the core subunits of nucleosome remodelling and deacetylation (NuRD) complexes. To determine if CHD5 forms a similar complex, we performed studies on nuclear extracts from NBLS, SY5Y (both with endogenous CHD5 expression), NLF (CHD5 null) and NLF cells stably transfected with CHD5 cDNA (wild-type and V5–histidine-tagged). Immunoprecipitation (IP) was performed with either CHD5 antibody or antibody to V5/histidine-tagged protein. We identified NuRD components both by GST–FOG1 (Friend Of GATA1) pull-down and by IP. We also performed MS/MS analysis to confirm the presence of CHD5 or other protein components of the NuRD complex, as well as to identify other novel proteins. CHD5 was clearly associated with all canonical NuRD components, including metastasis-associated protein (MTA)1/2, GATA zinc finger domain containing 2A (GATAD2A), histone deacetylase (HDAC)1/2, retinoblastoma-binding protein (RBBP)4/7 and methyl DNA-binding domain protein (MBD)2/3, as determined by Western blotting and MS/MS. Our data suggest CHD5 forms a NuRD complex similar to CHD4. However, CHD5–NuRD may also have unique protein associations that confer functional specificity and may contribute to normal development and to tumour suppression in NB and other cancers.

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“…Binding of the BPTF PHD finger to H3K4me3 stabilizes the nucleosomeremodeling NURF complex at chromatin, enhancing NURF-catalyzed nucleosome sliding and activation of developmental genes Wysocka et al 2006). The nucleosome remodeling and repressive activities of the deacetylase NuRD complex depend on concurrent binding of two PHD fingers of the CHD4 ATPase subunit to H3 or H3K9me3 (Mansfield et al 2011;Musselman et al , 2012bRamirez et al 2012). Interaction of the non-canonical PHD finger with H3K9me3 promotes localization of another ATP-dependent chromatin remodeler, ATRX, with heterochromatin (Dhayalan et al 2011;Eustermann et al 2011;Iwase et al 2011).…”

Section: Crosstalk To Dna Methylation and Chromatin Remodelingmentioning

confidence: 99%

PHD Fingers as Histone Readers

Gatchalian

Kutateladze

2015

Histone Recognition

Self Cite

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The plant homeodomain (PHD) finger is found in proteins implicated in fundamental biological processes, including transcription, replication, DNA damage repair, cell differentiation and survival. This small double-zinc-finger domain functions as an epigenetic effector or reader that binds to posttranslationally modified and unmodified histone H3 tails and recruits transcription factors, catalytic writers and erasers, nucleosome-remodeling complexes, and other components of the epigenetic machinery to specific genomic sites. In this chapter, we review the chromatin-binding mechanisms and biological outcomes associated with binding of the PHD fingers to histone ligands and discuss the structural bases for selectivity of this reader toward histone PTMs. IntroductionThe plant homeodomain (PHD) finger was discovered in the Arabidopsis protein HAT3.1 in 1993 (Schindler et al. 1993) and has since been found in a variety of proteins implicated in the regulation of chromatin structure and dynamics. The PHD finger is evolutionarily conserved and is present either as a single module or in multiple copies in 218 human proteins (SMART). The ~65-residue cysteinerich sequence of the PHD finger binds two zinc ions in a cross-braced manner. Although similar zinc-coordinating topology is seen in other double zinc fingers, including RING, FYVE, and MYND domains, the PHD finger can be distinguished by its canonical C4HC3 motif (and less common C4HC2H), as compared to the C3HC4 motif of RING, C5C/HC2 of FYVE, and C/HC4C/HHC of MYND. The primary sequences of the PHD fingers show low amino acid similarity;

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MBD2 and Multiple Domains of CHD4 Are Required for Transcriptional Repression by Mi-2/NuRD Complexes

Cited by 57 publications

References 57 publications

Interpreting the language of histone and DNA modifications

Interpreting the language of histone and DNA modifications

The tumour suppressor CHD5 forms a NuRD-type chromatin remodelling complex

PHD Fingers as Histone Readers

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