CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome

Batsukh, Tserendulam; Pieper, Lasse; Koszucka, Anna M.; Velsen, Nina von; Hoyer‐Fender, Sigrid; Elbracht, Miriam; Bergman, Jorieke E. H.; Hoefsloot, Lies H.; Pauli, Silke

doi:10.1093/hmg/ddq189

Cited by 74 publications

(82 citation statements)

References 30 publications

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“…CHD7-containing complexes have been characterized in a variety of cell types, including human ESCs (PBAF), HeLa cells (WDR4, FAM124B), mouse neural progenitors (SOX2 and other proteins), and cardiomyocytes (SMAD1/5/8 and Brg1) (29,32,(39)(40)(41)(42). The lack of interaction between CHD7 and RA suggests that instead of functioning in the same large complex, CHD7 may regulate nucleosome accessibility independent of RAR/RXR heterodimers.…”

Section: Discussionmentioning

confidence: 99%

CHD7 represses the retinoic acid synthesis enzyme ALDH1A3 during inner ear development

Yao¹,

Hill²,

Skidmore³

et al. 2018

JCI Insight

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Section: Discussionmentioning

confidence: 99%

CHD7 represses the retinoic acid synthesis enzyme ALDH1A3 during inner ear development

Yao¹,

Hill²,

Skidmore³

et al. 2018

JCI Insight

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“…Very little is known of CHD6 function, although reports suggest its involvement in processes such as human cancers (62)(63)(64). Mutations in the CHD7 gene are described as responsible for CHARGE syndrome, a complex neurological syndrome (65); since it interacts with CHD7, CHD8 might also be involved in CHARGE syndrome (66). The CHD8 tandem chromodomains bind specifically to histone H3 dimethylated at lysine 4 in vitro (67).…”

Section: Discussionmentioning

confidence: 99%

Influenza Virus and Chromatin: Role of the CHD1 Chromatin Remodeler in the Virus Life Cycle

Marcos-Villar

Pazo

Nieto

2016

J Virol

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Influenza A virus requires ongoing cellular transcription to carry out the cap-snatching process. Chromatin remodelers modify chromatin structure to produce an active or inactive conformation, which enables or prevents the recruitment of transcriptional complexes to specific genes; viral transcription thus depends on chromatin dynamics. Influenza virus polymerase associates with chromatin components of the infected cell, such as RNA polymerase II (RNAP II) or the CHD6 chromatin remodeler. Here we show that another CHD family member, CHD1 protein, also interacts with the influenza virus polymerase complex. CHD1 recognizes the H3K4me3 (histone 3 with a trimethyl group in lysine 4) histone modification, a hallmark of active chromatin. Downregulation of CHD1 causes a reduction in viral polymerase activity, viral RNA transcription, and the production of infectious particles. Despite the dependence of influenza virus on cellular transcription, RNAP II is degraded when viral transcription is complete, and recombinant viruses unable to degrade RNAP II show decreased pathogenicity in the murine model. We describe the CHD1-RNAP II association, as well as the parallel degradation of both proteins during infection with viruses showing full or reduced induction of degradation. The H3K4me3 histone mark also decreased during influenza virus infection, whereas a histone mark of inactive chromatin, H3K27me3, remained unchanged. Our results indicate that CHD1 is a positive regulator of influenza virus multiplication and suggest a role for chromatin remodeling in the control of the influenza virus life cycle. IMPORTANCEAlthough influenza virus is not integrated into the genome of the infected cell, it needs continuous cellular transcription to synthesize viral mRNA. This mechanism implies functional association with host genome expression and thus depends on chromatin dynamics. Influenza virus polymerase associates with transcription-related factors, such as RNA polymerase II, and with chromatin remodelers, such as CHD6. We identified the association of viral polymerase with another chromatin remodeler, the CHD1 protein, which positively modulated viral polymerase activity, viral RNA transcription, and virus multiplication. Once viral transcription is complete, RNAP II is degraded in infected cells, probably as a virus-induced mechanism to reduce the antiviral response. CHD1 associated with RNAP II and paralleled its degradation during infection with viruses that induce full or reduced degradation. These findings suggest that RNAP II degradation and CHD1 degradation cooperate to reduce the antiviral response. Influenza A virus contains eight single-stranded RNA segments of negative polarity (viral RNA [vRNA]) that form viral ribonucleoproteins (vRNP) by association with a trimeric polymerase complex that consists of the PA, PB1, and PB2 subunits and the nucleoprotein (NP). These vRNP are the functional units for RNA transcription and replication, which are restricted to the nucleus of the infected cell (1). For viral RNA r...

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“…CHD8, another CHD member belonging to the same subgroup as CHD7, is capable of forming a complex with WDR5, ASH2L, and RbBP5 in the absence of KMT2D (Thompson et al, 2008;Yates, Menon, Thompson, & Bochar, 2010). We demonstrated that CHD7 interacts with CHD8 (Batsukh et al, 2010) and that CHD7 is associated with members of the WAR complex suggesting that CHD7, KMT2D, and KDM6A work in the same nucleosome modifying and remodeling machinery, explaining the clinical overlap between CHARGE and Kabuki syndrome (Schulz, Freese, et al, 2014).…”

Section: Chd7 Protein Complexes and Their Function In Development Amentioning

confidence: 70%

CHARGEd with neural crest defects

Pauli

Bajpai

Borchers

2017

American J of Med Genetics Pt C

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Neural crest cells are highly migratory pluripotent cells that give rise to diverse derivatives including cartilage, bone, smooth muscle, pigment, and endocrine cells as well as neurons and glia. Abnormalities in neural crest‐derived tissues contribute to the etiology of CHARGE syndrome, a complex malformation disorder that encompasses clinical symptoms like coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, ear anomalies, and deafness. Mutations in the chromodomain helicase DNA‐binding protein 7 (CHD7) gene are causative of CHARGE syndrome and loss‐of‐function data in different model systems have firmly established a role of CHD7 in neural crest development. Here, we will summarize our current understanding of the function of CHD7 in neural crest development and discuss possible links of CHARGE syndrome to other developmental disorders.

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CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome

Cited by 74 publications

References 30 publications

CHD7 represses the retinoic acid synthesis enzyme ALDH1A3 during inner ear development

CHD7 represses the retinoic acid synthesis enzyme ALDH1A3 during inner ear development

Influenza Virus and Chromatin: Role of the CHD1 Chromatin Remodeler in the Virus Life Cycle

CHARGEd with neural crest defects

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