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FLASH GENE

Symbol

CTCFL

contributors: mct/pgu - updated : 13-04-2020

HGNC name	CCCTC-binding factor (zinc finger protein)-like
HGNC id	16234

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	29.69 kb     11 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	three promoters, designated A, B and C, corresponding to transcription start sites at -1447, -899 and -658 bp upstream of the first ATG,
	negatively regulated by DNA methylation and by CTCF and TP53
	three promoter blocks, the GATA/CCAAT box was determined to be a critical element of the core promoter, while the CpG islands and the BORIS-MS2 minisatellite region were found to act as regulators

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

text	varying promoter usage driving multiple transcripts could influence many aspects of epigenetic reprogramming in normal development and in tumorigenesis

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_080618 12 - 3493 NP_542185 - 663 - 2007 17957795 also called variant 1 NM_001269040 11 - 3601 NP_001255969 - 663 - 2007 17957795 variant A1 having promoter A preferentially used upon activation of BORIS during tumorigenesis variant A2 - - 3701 isoform A2 - 663 - 2007 17957795 having promoter A preferentially used upon activation of BORIS during tumorigenesis NM_001269046 10 - 3897 NP_001255975 - 613 - 2007 17957795 variant A3 having promoter A preferentially used upon activation of BORIS during tumorigenesis NM_001269041 10 - 4073 NP_001255970 - 663 - 2007 17957795 variant C1 having promoter C preferentially used upon activation of BORIS during tumorigenesis NM_001269042 11 - 3598 NP_001255971 - 662 - 2007 17957795 NM_001269047 10 - 3002 NP_001255976 - 573 - 2007 17957795 NM_001269045 10 - 2955 NP_001255974 - 627 - 2007 17957795 NM_001269051 5 - 1513 NP_001255980 - 404 - 2007 17957795 NM_001269050 10 - 2295 NP_001255979 - 422 - 2007 17957795 NM_001269055 8 - 2168 NP_001255984 - 299 - 2007 17957795 NM_001269043 12 - 2499 NP_001255972 - 700 - 2007 17957795 NM_001269049 10 - 2288 NP_001255978 - 460 - 2007 17957795 NM_001269054 10 - 2077 NP_001255983 - 403 - 2007 17957795 NM_001269052 4 - 1985 NP_001255981 - 404 - 2007 17957795

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Reproductive male system testis       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow

cells

System Cell Pubmed Species Stage Rna symbol Reproductive germ cell Reproductive spermatocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	eleven zinc fingers flanked by polypeptides of unknown structure and function, an 11ZF domain that is highly similar to the 11ZF domain of CTCF
	unstructured terminal segments of CTCF and CTCFL that could recruit different binding partners to chromosomes

HOMOLOGY

intraspecies

paralog to CTCF

Homologene

FAMILY	cancer testis antigen (CTA) family
	CTCF zinc-finger protein family

CATEGORY

regulatory , tumor suppressor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm,nuclear bodies
	intracellular,nucleus,nucleolus
text	cytoplasm of spermatocytes
	is confined to the nucleolus and other euchromatin domains, but also localises to interphase centrosomes suggesting a role in the cell cycle
	in the nucleus, is particularly enriched in the nucleolus, a crucial compartment for ribosomal RNA and RNA metabolism

basic FUNCTION	involved in different aspects of gene regulation including promoter activation or repression, hormone-responsive gene silencing, methylation- dependent chromatin insulation, and genomic imprinting
	possible involvement in the establishment, progression and maintenance of breast tumours
	has acquired testis-specific functions in mammalian organisms
	DNA-binding factor that regulates the transcriptional program of mammalian male germ cells
	plays important physiological functions in progression of spermatogenesis by regulating expression of a testis-specific splicing variant of cerebroside sulfotransferase
	directly involved in activation of PRSS50 expression by binding to the promoter region
	potential role for BORIS in coordinating S phase events with mitosis
	is likely involved in gene expression at both the transcriptional and post-transcriptional levels
	is associated with cancer stem cell-enriched populations of several epithelial tumor cells and the different phenotypes depend on the origin of tumor cells
	CTCFL is enriched at transcriptional start sites and regions bound by transcription factors
	plays crucial roles during spermatogenesis and production of sperm
	is involved in the regulation of cancer stem cells (CSCs) cellular and molecular features such as self-renewal, chemo-resistance, tumorigenicity, sphere-forming ability, and migration capacity
	DNA binding protein which is involved in tumorigenesis
	pro-invasive role for CTCFL in melanoma via transcriptional reprogramming

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

binding

RNA

small molecule	metal binding,
	Zn2+

protein	CTCFL positively regulates MAGEA2, MAGEA3, MAGEA4 by binding and inducing a shift to a more open chromatin conformation with promoter demethylation for MAGEA3 or independent of promoter demethylation in case of MAGEA2 and MAGEA4
	directly responsible for the transcriptional activation of PRSS50
	in cancer cells, key role for CTCFL as the main mediator of transcriptional deregulation of NOTCH3
	CTCFL and Sp1 have opposite effects on the regulation of MAGEA1 gene expression
	interaction between MAGEA1 and CTCF, which is required for the binding of MAGEA1 to the CTCFL promoter and is critical for the recruitment of DNMT3A
	binds near the promoter of TFGB1, a well-recognized factor involved in the transition towards an invasive state, which coincided with increased expression of TGFB1

cell & other

REGULATION

inhibited by

MAGEA1 that inhibits the expression of CTCL via increased promoter methylation

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in juvenile angiofibroma in the posterior nasal cavity of adolescent males tumoral     --other   aberrantly expressed in melanoma tumoral     --over   in high-grade epithelial ovarian cancer

Susceptibility

Variant & Polymorphism

Candidate gene	candidate protein for the elusive epigenetic reprogramming factor acting in the male germ line
	potential practical applications as a molecular biomarker of breast cancer
Marker	aberrant CTCFL hypomethylation is a promising biomarker for the prognosis of hepatocellular carcinoma
Therapy target	has the potential to be used as a prognostic biomarker and to yield novel drug targets among the genes CTCFL controls in serous ovarian cancer (SOC) patients

ANIMAL & CELL MODELS

Mice homozygous for the null allele had a defect in spermatogenesis that resulted in small testes associated with increased cell death