CHD7 functions in the nucleolus as a positive regulator of ribosomal RNA biogenesis

Zentner, Gabriel E.; Hurd, E. A.; Schnetz, Michael P.; Handoko, Lusy; Wang, Chuanping; Wang, Zhenghe; Wei, Chia‐Lin; Tesar, Paul J.; Hatzoglou, Maria; Martin, Donna M.; Scacheri, Peter C.

doi:10.1093/hmg/ddq265

Cited by 91 publications

(96 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…29,30 They also suggest that CHD7 binds to several sites on the DNA with different protein complexes in a tissue-and time-specific manner, regulating various target genes. 29,30 The continuum of influences of CHD7 at different levels and in different cell types could explain the clinical variability seen in different organ systems of individuals with CHARGE syndrome, including the broad spectrum of heart defects. 31,32 CHD7 probably regulates the expression of cardiac transcription factors by chromatin remodeling.…”

Section: Discussionmentioning

confidence: 99%

The Cardiac Phenotype in Patients With a CHD7 Mutation

Corsten‐Janssen

Kerstjens-Frederikse

Sarvaas

et al. 2013

Circ Cardiovasc Genet

View full text Add to dashboard Cite

Background— Loss-of-function mutations in CHD7 cause Coloboma, Heart Disease, Atresia of Choanae, Retardation of Growth and/or Development, Genital Hypoplasia, and Ear Abnormalities With or Without Deafness (CHARGE) syndrome, a variable combination of multiple congenital malformations including heart defects. Heart defects are reported in 70% to 92% of patients with a CHD7 mutation, but most studies are small and do not provide a detailed classification of the defects. We present the first, detailed, descriptive study on the cardiac phenotype of 299 patients with a CHD7 mutation and discuss the role of CHD7 in cardiac development. Methods and Results— We collected information on congenital heart defects in 299 patients with a pathogenic CHD7 mutation, of whom 220 (74%) had a congenital heart defect. Detailed information on the heart defects was available for 202 of these patients. We classified the heart defects based on embryonic cardiac development and compared the distribution to 1007 equally classified nonsyndromic heart defects of patients registered by EUROCAT, a European Registry of Congenital Anomalies. Heart defects are highly variable in patients with CHD7 mutations, but atrioventricular septal defects and conotruncal heart defects are over-represented. Sex did not have an effect on the presence of heart defects, but truncating CHD7 mutations resulted in a heart defect significantly more often than missense or splice-site mutations (χ 2 , P <0.001). Conclusions— CHD7 plays an important role in cardiac development, given that we found a wide range of heart defects in 74% of a large cohort of patients with a CHD7 mutation. Conotruncal defects and atrioventricular septal defects are over-represented in patients with CHD7 mutations compared with patients with nonsyndromic heart defects.

show abstract

Section: Discussionmentioning

confidence: 99%

The Cardiac Phenotype in Patients With a CHD7 Mutation

Corsten‐Janssen

Kerstjens-Frederikse

Sarvaas

et al. 2013

Circ Cardiovasc Genet

View full text Add to dashboard Cite

show abstract

“…CHD7 is a transcriptional regulator that binds to enhancer elements in the nucleoplasm, and also functions as a positive regulator of rRNA biogenesis in the nucleolus (171).…”

Section: Syndromes With (Usually) Normal Head Circumferencementioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

Wit

Oostdijk

Losekoot

et al. 2016

European Journal of Endocrinology

148

132

View full text Add to dashboard Cite

The fast technological development, particularly single nucleotide polymorphism array, array-comparative genomic hybridization, and whole exome sequencing, has led to the discovery of many novel genetic causes of growth failure. In this review we discuss a selection of these, according to a diagnostic classification centred on the epiphyseal growth plate. We successively discuss disorders in hormone signalling, paracrine factors, matrix molecules, intracellular pathways, and fundamental cellular processes, followed by chromosomal aberrations including copy number variants (CNVs) and imprinting disorders associated with short stature. Many novel causes of GH deficiency (GHD) as part of combined pituitary hormone deficiency have been uncovered. The most frequent genetic causes of isolated GHD are GH1 and GHRHR defects, but several novel causes have recently been found, such as GHSR, RNPC3, and IFT172 mutations. Besides well-defined causes of GH insensitivity (GHR, STAT5B, IGFALS, IGF1 defects), disorders of NFkB signalling, STAT3 and IGF2 have recently been discovered. Heterozygous IGF1R defects are a relatively frequent cause of prenatal and postnatal growth retardation. TRHA mutations cause a syndromic form of short stature with elevated T 3 /T 4 ratio. Disorders of signalling of various paracrine factors (FGFs, BMPs, WNTs, PTHrP/IHH, and CNP/NPR2) or genetic defects affecting cartilage extracellular matrix usually cause disproportionate short stature. Heterozygous NPR2 or SHOX defects may be found in w3% of short children, and also rasopathies (e.g., Noonan syndrome) can be found in children without clear syndromic appearance. Numerous other syndromes associated with short stature are caused by genetic defects in fundamental cellular processes, chromosomal abnormalities, CNVs, and imprinting disorders.

show abstract

“…Chromatin immunoprecipitation and subsequent sequencing (CHIP‐seq) studies demonstrate that CHD7 is recruited preferentially to distal gene regulatory elements, or enhancers, implying a role for CHD7 in enhancer‐regulated gene transcription (Engelen et al, 2011; Schnetz et al, 2009; Zentner et al, 2010). In vitro studies have provided direct experimental evidence for the ATP‐dependent nucleosome remodeling activity of CHD7.…”

Section: Introductionmentioning

confidence: 99%

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

Whittaker

Kasah

Donovan

et al. 2017

American J of Med Genetics Pt C

View full text Add to dashboard Cite

Mutations in the gene encoding the ATP dependent chromatin‐remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital‐urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar hypoplasia and distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model. We describe specific alterations in the precise spatio‐temporal sequence of fissure formation during perinatal cerebellar development responsible for these foliation anomalies. The altered cerebellar foliation pattern in Chd7 haploinsufficient mice show some similarities to those reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we propose that mutations or polymorphisms in these genes may modify the cerebellar phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome indicate that a careful analysis of cerebellar foliation may be warranted in patients with CHARGE syndrome, particularly in patients with cerebellar hypoplasia and developmental delay.

show abstract

CHD7 functions in the nucleolus as a positive regulator of ribosomal RNA biogenesis

Cited by 91 publications

References 55 publications

The Cardiac Phenotype in Patients With a CHD7 Mutation

The Cardiac Phenotype in Patients With a CHD7 Mutation

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

Contact Info

Product

Resources

About