Download Gene Section CHD5 (Chromodomain-helicase-DNA binding protein 5) Atlas of Genetics and Cytogenetics

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Gene Section
Mini Review
CHD5 (Chromodomain-helicase-DNA binding
protein 5)
Garrett M Brodeur, Peter S White
Children's Hospital of Philadelphia, Oncology Research, CTRB Rm. 3018, 3501 Civic Center Blvd,
Philadelphia, PA 19104, USA (GMB); Children's Hospital of Philadelphia, Center for Biomedical
Informatics, Rm. 1407 CHOP North, 34th St and Civic Center Blvd, Philadelphia, PA 19104, USA (PSW)
Published in Atlas Database: January 2010
Online updated version : http://AtlasGeneticsOncology.org/Genes/CHD5ID44521ch1p36.html
DOI: 10.4267/2042/44864
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Gene is encoded by 42 exons, spanning 78331 bp.
includes a predicted DEAH-box type helicase domain
(703-999) and a putative SNF2 domain (1054-1138).
DEAH ATP helicases are ATP-dependent and are
usually associated with nucleic acid unwinding. SNF2
domains are commonly observed in, although not
restricted to, proteins involved in chromatin unwinding,
DNA repair and recombination, and transcriptional
regulation. A number of potential nuclear localization
signals are also present (50-67, 54-71, 97-114, 100117, 240-257, 253-270, 918-935) (Thompson et al.,
2003).
Transcription
Expression
The CHD5 cDNA sequence spans 9646 bp, with a 5'
UTR of 100 bp, a single open reading frame of 5865
bp, and a 3' UTR of 3681 bp (Thompson et al., 2003).
Detectable expression of CHD5 was limited to all
neural-derived tissues (fetal brain, total brain,
cerebellum) and adrenal gland, with no expression
detected in placenta, liver, fetal liver, spleen, bone
marrow, thyroid, thymus, salivary gland, stomach,
pancreas, small intestine, colon, or prostate (Thompson
et al., 2003; Okawa et al., 2008).
Identity
Other names: DKFZp434N231; KIAA0444
HGNC (Hugo): CHD5
Location: 1p36.31
DNA/RNA
Description
Pseudogene
None known.
Protein
Localisation
Description
Intracellular expression is preferentially
(unpublished observations, GMB).
The 5' portion of CHD5 is predicted to contain two
zinc-fingers of the PHD class (amino-acid positions
345-390 and 418-463), followed closely by two
chromodomains (510-525 and 596-625). PHD zincfinger motifs are thought to play roles in chromatinassociated
transcriptional
regulation,
whereas
chromodomains are frequently observed in proteins
involved in recruitment of transcriptional regulatory
complexes. The central portion of the protein
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(10)
nuclear
Function
CHD family proteins are thought to play a role in
chromatin remodeling. CHD5 is most homologous to
CHD3 and CHD4, which participate in the formation of
a Nucleosome Remodeling and Deacetylation (NuRD)
complex, in association with other proteins. This
complex is generally thought to repress transcription.
934
CHD5 (Chromodomain-helicase-DNA binding protein 5)
Brodeur GM, White PS
The functional domains of the chromodomain-helicase-DNA binding protein 5 (CHD5) are shown above. There are two PHD type zinc
fingers, two chromodomains, a split DEAH-box ATP-helicase domain, and a poorly defined DNA binding domain.
region of consistent deletion in 17 glioma cell lines
(Law et al., 2005). Loss of CHD5 expression is
associated with deletion of 1p36 in a panel of 54 glial
tumors (Bagchi et al., 2007). These data are consistent
with a role for CHD5 as a tumor suppressor gene in
these tumors.
Homology
Strongest homology to CHD3 and CHD4, with weaker
homology to CHD1, CHD2, CHD6, CHD7, CHD8 and
CHD9.
Mutations
Melanoma
Note
No examples of homozygous inactivation have been
identified, and no nonsense or frameshift mutations
have been identified in any cancers to date. Several
missense mutations have been detected, but it is unclear
if any of these have an effect on the function of the
protein (Okawa et al., 2008; Fujita et al., 2008; Ng et
al., 2008).
Note
A subset of malignant melanoma families show linkage
to 1p36, and CHD5 is a tumor suppressor gene that
maps to this region. However, screening of CHD5 for
mutations in eight melanoma-prone families linked to
1p36 revealed no deleterious coding or splice site
mutations (Ng et al., 2008). This suggests that CHD5 is
not a major melanoma susceptibility gene, at least in
the families screened.
Implicated in
Ovarian cancer
Neuroblastoma
Note
Mutation and methylation analysis of CHD5 gene was
undertaken in 123 ovarian cancers, whereas no such
mutations were identified in 60 primary breast cancers.
Somatic heterozygous missense mutations were
identified in 3 samples, and promoter methylation was
identified in another 3 of 45 samples tested (Gorringe
et al., 2008). These data suggest that CHD5 may play a
role as a tumor suppressor gene in a subset of ovarian
cancers, but there may be other suppressors on 1p36 as
well.
Note
CHD5, a new member of the chromodomain gene
family, is preferentially expressed in the nervous
system (Thompson et al., 2003). CHD5 maps to
1p36.3, a region of consistent deletion in
neuroblastoma and other tumors (White et al., 2005).
CHD5 is one of 23 genes that map to the 800 Kb region
of consistent deletion on 1p36.3 in an analysis of over
1,200 primary neuroblastomas (Okawa et al., 2008).
Functional analysis of CHD5 after transfection into
neuroblastoma cell lines demonstrates that CHD5
functions as a tumor suppressor gene, suppressing both
clonogenicity and tumorigenicity. The promoter was
methylated especially between -780 and -450 in
neuroblastoma cell lines with 1p36 deletions, but not
those with two copies of CHD5. Furthermore, high
CHD5 expression is highly correlated with favorable
clinical and biological risk features as well as outcome
in a panel of 101 primary tumors (Fujita et al., 2008).
These data suggest that CHD5 is a bona fide tumor
suppressor gene in neuroblastomas. Deletion of 1p36 is
associated with loss of CHD5 expression, and the
CHD5 promoter is preferentially methylated in lines
with 1p36 deletion. Furthermore, low CHD5 expression
is associated with a worse outcome in neuroblastoma
patients.
Colorectal cancer
Note
The methylation status of a set of cancer-related genes
was studied in 102 colon cancers from Iranian and
African-American populations (51 each). The
methylation status of the promoters of three genes
(CHD5, ICAM5 and GPNMB) was significantly higher
in cancers from the African-American population
compared to the Iranian patients (Mokarram et al.,
2009). This suggests that these genes may play a role in
the incidence or aggressiveness of colorectal cancer in
this population.
Gastric cancer
Note
The methylation status of the CHD5 promoter was
examined in 15 primary gastric cancers and 7 gastric
cancer cell lines. CHD5 expression was downregulated
in 7/7 cell lines, and methylation of the promoter was
Gliomas
Note
CHD5 is one of several genes that maps to the 700 Kb
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(10)
935
CHD5 (Chromodomain-helicase-DNA binding protein 5)
Brodeur GM, White PS
Bagchi A, Papazoglu C, Wu Y, Capurso D, Brodt M, Francis D,
Bredel M, Vogel H, Mills AA. CHD5 is a tumor suppressor at
human 1p36. Cell. 2007 Feb 9;128(3):459-75
found in all 7 lines, and a similar correlation was found
in 11/15 primary tumors. Ectopic expression of CHD5
led to significant growth inhibition. These results
suggest that CHD5 plays a role as a tumor suppressor
gene in gastric cancer, and its expression may be downregulated epigenetically.
Fujita T, Igarashi J, Okawa ER, Gotoh T, Manne J, Kolla V,
Kim J, Zhao H, Pawel BR, London WB, Maris JM, White PS,
Brodeur GM. CHD5, a tumor suppressor gene deleted from
1p36.31 in neuroblastomas. J Natl Cancer Inst. 2008 Jul
2;100(13):940-9
Colon cancer, breast cancer, gliomas
Gorringe KL, Choong DY, Williams LH, Ramakrishna M,
Sridhar A, Qiu W, Bearfoot JL, Campbell IG. Mutation and
methylation analysis of the chromodomain-helicase-DNA
binding 5 gene in ovarian cancer. Neoplasia. 2008
Nov;10(11):1253-8
Note
The promoter of all nine current members of the CHD
family were analyzed for methylation, and only the
CHD5 promoter showed CpG hypermethylation in a
subset of primary cancers, especially colon cancer,
breast cancer and gliomas (Mulero-Navarro and
Esteller, 2008). Thus, epigenetic inactivation of CHD5
expression may contribute to the pathogenesis of
various cancers.
Mulero-Navarro S, Esteller M. Chromatin remodeling factor
CHD5 is silenced by promoter CpG island hypermethylation in
human cancer. Epigenetics. 2008 Jul-Aug;3(4):210-5
Ng D, Yang XR, Tucker MA, Goldstein AM. Mutation screening
of CHD5 in melanoma-prone families linked to 1p36 revealed
no deleterious coding or splice site changes. BMC Res Notes.
2008 Sep 19;1:86
Breakpoints
Okawa ER, Gotoh T, Manne J, Igarashi J, Fujita T, Silverman
KA, Xhao H, Mosse YP, White PS, Brodeur GM. Expression
and sequence analysis of candidates for the 1p36.31 tumor
suppressor gene deleted in neuroblastomas. Oncogene. 2008
Jan 31;27(6):803-10
Note
None known.
References
Mokarram P, Kumar K, Brim H, Naghibalhossaini F, Saberifiroozi M, Nouraie M, Green R, Lee E, Smoot DT, Ashktorab H.
Distinct high-profile methylated genes in colorectal cancer.
PLoS One. 2009 Sep 11;4(9):e7012
Thompson PM, Gotoh T, Kok M, White PS, Brodeur GM.
CHD5, a new member of the chromodomain gene family, is
preferentially expressed in the nervous system. Oncogene.
2003 Feb 20;22(7):1002-11
Wang X, Lau KK, So LK, Lam YW. CHD5 is down-regulated
through promoter hypermethylation in gastric cancer. J Biomed
Sci. 2009 Oct 19;16:95
Law ME, Templeton KL, Kitange G, Smith J, Misra A,
Feuerstein BG, Jenkins RB. Molecular cytogenetic analysis of
chromosomes 1 and 19 in glioma cell lines. Cancer Genet
Cytogenet. 2005 Jul 1;160(1):1-14
This article should be referenced as such:
Brodeur GM, White PS. CHD5 (Chromodomain-helicase-DNA
binding protein 5). Atlas Genet Cytogenet Oncol Haematol.
2010; 14(10):934-936.
White PS, Thompson PM, Gotoh T, Okawa ER, Igarashi J, Kok
M, Winter C, Gregory SG, Hogarty MD, Maris JM, Brodeur GM.
Definition and characterization of a region of 1p36.3
consistently deleted in neuroblastoma. Oncogene. 2005 Apr
14;24(16):2684-94
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(10)
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