Tle4 transducin-like enhancer of split 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Tle4provided by MGI
Official Full Name: transducin-like enhancer of split 4provided by MGI
Primary source: MGI:MGI:104633
See related: Ensembl:ENSMUSG00000024642 AllianceGenome:MGI:104633
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Bce1; Grg4; Bce-1; grg-4; ESTM13; ESTM14; 5730411M05Rik
Summary: Enables DNA-binding transcription factor binding activity; chromatin binding activity; and transcription corepressor activity. Involved in negative regulation of transcription, DNA-templated. Acts upstream of or within Wnt signaling pathway; cellular response to leukemia inhibitory factor; and negative regulation of transcription by RNA polymerase II. Located in nucleus. Is expressed in several structures, including central nervous system; embryo ectoderm; embryo mesenchyme; genitourinary system; and peripheral nervous system ganglion. Orthologous to human TLE4 (TLE family member 4, transcriptional corepressor). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in whole brain E14.5 (RPKM 15.3), CNS E18 (RPKM 14.5) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 19 A; 19 9.11 cM

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	19	NC_000085.7 (14425434..14575542, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	19	NC_000085.6 (14448072..14598183, complement)

Chromosome 19 - NC_000085.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

TLE3 and TLE4-coordinated colonic macrophage-CD4[+] T cell crosstalk maintains intestinal immune homeostasis.
Title: TLE3 and TLE4-coordinated colonic macrophage-CD4(+) T cell crosstalk maintains intestinal immune homeostasis.
Groucho co-repressor proteins regulate beta cell development and proliferation by repressing Foxa1 in the developing mouse pancreas.
Title: Groucho co-repressor proteins regulate β cell development and proliferation by repressing Foxa1 in the developing mouse pancreas.
The authors found that TLE4 physically interacted with Hes1 (hairy and enhancer of split 1) and inhibited expression of IL-6 and IL-12, two key pro-inflammatory cytokines, in a pattern highly similar to inhibitory action of Hes1.
Title: TLE4 acts as a corepressor of Hes1 to inhibit inflammatory responses in macrophages.
These findings indicate that Tle corepressors are differentially partitioned to Runx and Tcf/Lef complexes to instruct CD8(+) lineage choice and cooperatively establish CD8(+) T cell identity, respectively.
Title: Tle corepressors are differentially partitioned to instruct CD8(+) T cell lineage choice and identity.
These results demonstrated that TLE4 might play important regulatory roles in cellular proliferation and EMT process in HCC.
Title: Down-regulation of Transducin-Like Enhancer of Split protein 4 in hepatocellular carcinoma promotes cell proliferation and epithelial-Mesenchymal-Transition.
Tle4 KO mice are runted, have defects in bone development, bone marrow aplasia. Have leukocytopenia, b-cell lymphoma and reductions in stem cells by 2 weeks. Die by 4 weeks.
Title: The corepressor Tle4 is a novel regulator of murine hematopoiesis and bone development.
TLE3/4 activity is essential for early differentiation where it acts to suppress the pluripotency network, allowing for the initiation of lineage specific gene expression programs
Title: Gro/TLE enables embryonic stem cell differentiation by repressing pluripotent gene expression.
Blimp1-dependent recruitment of Tle4 to the Ifng locus causes epigenetic silencing of the expression of the Ifng gene in anergic TH1 cells.
Title: Tle4 regulates epigenetic silencing of gamma interferon expression during effector T helper cell tolerance.
Grg4 is an interacting partner for Cux1 and suggest a mechanism of p27(kip1) repression by Cux1 during kidney development.
Title: The homeodomain protein Cux1 interacts with Grg4 to repress p27 kip1 expression during kidney development.
Gbx2 and Otx2 interact with the WD40 domain of Groucho/Tle corepressors
Title: Gbx2 and Otx2 interact with the WD40 domain of Groucho/Tle corepressors.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Gene trapped (2)
Targeted (4) 1 citation
Endonuclease-mediated (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH118382 (e-PCR)
- UniSTS:160813

D19Mit116 (e-PCR), detects polymorphism
- UniSTS:128330

Tle4 (e-PCR), detects polymorphism
- UniSTS:527580

AA792082 (e-PCR)
- UniSTS:166128

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription corepressor activity	IBA Inferred from Biological aspect of Ancestor more info
enables transcription corepressor activity	IDA Inferred from Direct Assay more info	PubMed
enables transcription corepressor activity	IGI Inferred from Genetic Interaction more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cellular response to leukemia inhibitory factor	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of DNA-templated transcription	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of canonical Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of beta-catenin-TCF complex	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IC Inferred by Curator more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of transcription regulator complex	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: transducin-like enhancer protein 4

Names: B lymphocyte gene 1; groucho-related protein 4; transducin-like enhancer of split 4, homolog of Drosophila E(spl)

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001302947.2 → NP_001289876.1 transducin-like enhancer protein 4 isoform 1

See identical proteins and their annotated locations for NP_001289876.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AC122202, AC125315

UniProtKB/TrEMBL

F6ZBY9, Q3UY41

Conserved Domains (3) summary

cd00200
Location:487 → 771

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:491 → 530

7WD40; WD40 repeat [structural motif]

pfam03920
Location:16 → 139

TLE_N; Groucho/TLE N-terminal Q-rich domain
NM_001302950.2 → NP_001289879.1 transducin-like enhancer protein 4 isoform 3

See identical proteins and their annotated locations for NP_001289879.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon in the 5' coding region compared to variant 1. This results in a shorter protein (isoform 3), compared to isoform 1.

Source sequence(s)

AC122202, AC125315

UniProtKB/TrEMBL

F6ZBY9

Conserved Domains (3) summary

cd00200
Location:462 → 746

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:466 → 505

7WD40; WD40 repeat [structural motif]

pfam03920
Location:16 → 103

TLE_N; Groucho/TLE N-terminal Q-rich domain
NM_001302951.2 → NP_001289880.1 transducin-like enhancer protein 4 isoform 4

Status: VALIDATED

Description

Transcript Variant: This variant (4) uses an alternate 5'-terminal exon, which results in a distinct 5' UTR and use of an alternate start codon, compared to variant 1. The encoded protein (isoform 4) is shorter and has a distinct N-terminus compared to isoform 1.

Source sequence(s)

AC122202, AC125315

UniProtKB/TrEMBL

F6ZBY9

Conserved Domains (3) summary

cd00200
Location:485 → 769

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:489 → 528

7WD40; WD40 repeat [structural motif]

pfam03920
Location:14 → 137

TLE_N; Groucho/TLE N-terminal Q-rich domain
NM_011600.4 → NP_035730.2 transducin-like enhancer protein 4 isoform 2

See identical proteins and their annotated locations for NP_035730.2

Status: VALIDATED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. It encodes isoform 2 which is shorter by one amino acid compared to isoform 1.

Source sequence(s)

AC122202, AC125315

Consensus CDS

CCDS50399.1

UniProtKB/Swiss-Prot

Q62441, Q9JKQ9

UniProtKB/TrEMBL

F6ZBY9

Related

ENSMUSP00000057527.8, ENSMUST00000052011.15

Conserved Domains (3) summary

cd00200
Location:486 → 770

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:490 → 529

7WD40; WD40 repeat [structural motif]

pfam03920
Location:16 → 138

TLE_N; Groucho/TLE N-terminal Q-rich domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000085.7 Reference GRCm39 C57BL/6J

Range

14425434..14575542 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006526913.2 → XP_006526976.1 transducin-like enhancer protein 4 isoform X2

See identical proteins and their annotated locations for XP_006526976.1

UniProtKB/TrEMBL

F6ZBY9

Conserved Domains (3) summary

cd00200
Location:461 → 745

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:465 → 504

7WD40; WD40 repeat [structural motif]

pfam03920
Location:8 → 113

TLE_N; Groucho/TLE N-terminal Q-rich domain
XM_030250862.2 → XP_030106722.1 transducin-like enhancer protein 4 isoform X1

UniProtKB/TrEMBL

F6ZBY9

Conserved Domains (3) summary

cd00200
Location:484 → 768

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:488 → 527

7WD40; WD40 repeat [structural motif]

pfam03920
Location:14 → 136

TLE_N; Groucho/TLE N-terminal Q-rich domain
XM_030250864.2 → XP_030106724.1 transducin-like enhancer protein 4 isoform X4

UniProtKB/TrEMBL

F6ZBY9

Conserved Domains (3) summary

cd00200
Location:459 → 743

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:463 → 502

7WD40; WD40 repeat [structural motif]

pfam03920
Location:14 → 107

TLE_N; Groucho/TLE N-terminal Q-rich domain
XM_030250863.2 → XP_030106723.1 transducin-like enhancer protein 4 isoform X3

UniProtKB/TrEMBL

F6ZBY9

Conserved Domains (3) summary

cd00200
Location:460 → 744

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:464 → 503

7WD40; WD40 repeat [structural motif]

pfam03920
Location:14 → 101

TLE_N; Groucho/TLE N-terminal Q-rich domain
XM_006526914.5 → XP_006526977.1 transducin-like enhancer protein 4 isoform X5

UniProtKB/TrEMBL

Q80TG4

Conserved Domains (3) summary

cd00200
Location:366 → 650

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:370 → 409

7WD40; WD40 repeat [structural motif]

pfam03920
Location:1 → 18

TLE_N; Groucho/TLE N-terminal Q-rich domain