====== CHD7 ======

[[Chromodomain]]-[[helicase]]-DNA-[[binding protein]] 7 also known as [[ATP]]-dependent helicase CHD7 is an enzyme that in humans is encoded by the CHD7 gene.

CHD7 is an ATP-dependent [[chromatin]] remodeler homologous to the Drosophila trithorax-group protein Kismet.Mutations in CHD7 are associated with [[CHARGE syndrome]]
----
[[Tumorigenic]] and non-neoplastic [[tissue]] [[injury]] occurs via the ischemic [[microenvironment]] defined by low [[oxygen]], [[pH]], and [[nutrient]]s due to [[blood]] supply malfunction. Ischemic conditions exist within regions of pseudopalisading [[necrosis]], a pathological hallmark of [[glioblastoma]] (GBM), the most common primary malignant brain tumor in adults. To recapitulate the physiologic microenvironment found in GBM tumors and tissue injury, Boyd et al., from [[Birmingham]] [[Alabama]] developed an in vitro ischemic model and identified chromodomain helicase DNA binding protein 7 (CHD7) as a novel ischemia-regulated gene. Point [[mutation]]s in the CHD7 gene are causal in [[CHARGE syndrome]], a CNS developmental disorder, and interrupt the epigenetic functions of CHD7 in regulating [[neural stem cell]] maintenance and development. Using this ischemic system, they observed microenvironment-mediated decreases in CHD7 expression in [[brain tumor]] initiating cells and neural stem cells. Validating the approach, CHD7 was suppressed in the perinecrotic niche of GBM patient and [[xenograft]] sections, and an interrogation of patient gene expression datasets determined correlations between low CHD7, increasing [[glioma grade]] and worse patient [[outcome]]s. Segregation of GBM by molecular subtype revealed a novel observation that CHD7 expression is elevated in [[proneural]] vs [[mesenchymal glioblastoma]]. Genetic targeting of CHD7 and subsequent gene [[ontology]] analysis of [[RNA sequencing]] data indicated [[angiogenesis]] as a primary biological function affected by CHD7 expression changes. They validated this finding in tube formation assays and [[vessel]] formation in [[orthotopic]] GBM models. Together, this data provide further understanding of [[molecular]] responses to ischemia and a novel function of CHD7 in regulating angiogenesis in both neoplastic and non-neoplastic systems. 

Inactivating [[mutation]]s in the epigenetic modifier chromodomain helicase DNA binding protein 7 (CHD7) are associated with [[CHARGE syndrome]], a disorder causing [[Coloboma]], Heart defects, Atresia choanae, growth Retardation, Genital abnormalities, and Ear abnormalities. 

They find for the first time that ischemic microenvironments repress CHD7 levels in neural progenitors and brain tumor initiating cells/cancer stem cells. This novel results also demonstrate that reduced levels of CHD7 in neural progenitors or brain tumor initiating cells increase angiogenesis. They believed that this data may have important implications for development, [[stem cell]]s, and [[cancer]]
((Boyd NH, Walker K, Ayokanmbi A, Gordon ER, Whetsel J, Smith CM, Sanchez RG,
Lubin F, Chakraborty A, Tran AN, Herting C, Hambardzumyan D, Yancey Gillespie G, 
Hackney JR, Cooper SJ, Jiao K, Hjelmeland AB. [[CHD7]] is Suppressed in the
Perinecrotic/Ischemic [[Microenvironment]] and is a Novel Regulator of [[Glioblastoma]]
[[Angiogenesis]]. Stem Cells. 2019 Jan 10. doi: 10.1002/stem.2969. [Epub ahead of
print] PubMed PMID: 30629778.
)).
----
Badodi et al., described molecular convergence between [[BMI1]] and CHD7 in the initiation of [[medulloblastoma]]. Identified in a functional genomic screen in mouse models, a BMI1High;CHD7Low expression signature within medulloblastoma characterizes patients with poor overall survival. 

They showed that BMI1-mediated repression of the ERK1/2 pathway leads to increased proliferation and tumor burden in primary human MB cells and in a xenograft model, respectively. They provided evidence that repression of the ERK inhibitor [[DUSP4]] by [[BMI1]] is dependent on a more accessible chromatin configuration in G4 MB cells with low CHD7 expression. These findings extend current knowledge of the role of BMI1 and CHD7 in medulloblastoma pathogenesis, and they raise the possibility that pharmacological targeting of BMI1 or ERK may be particularly indicated in a subgroup of MB with low expression levels of CHD7
((Badodi S, Dubuc A, Zhang X, Rosser G, Da Cunha Jaeger M, Kameda-Smith MM,
Morrissy AS, Guilhamon P, Suetterlin P, Li XN, Guglielmi L, Merve A, Farooq H,
Lupien M, Singh SK, Basson MA, Taylor MD, Marino S. Convergence of BMI1 and CHD7 
on ERK Signaling in Medulloblastoma. Cell Rep. 2017 Dec 5;21(10):2772-2784. doi: 
10.1016/j.celrep.2017.11.021. PubMed PMID: 29212025; PubMed Central PMCID:
PMC5732319.
)).