1946 syntynyt Tampereella
Ylioppilastutkinto 1964 Lempäälä
Lääketietaan kandidaatti 1966 Turun yliopisto
Lääketieteen lisensiaatti 1972 Turun Yliopisto
Dietetiikan opiskelu 1998 - 2001 Göteborgin Yliopisto
Eläkkeelle 2010
Atoh-expressing retinal progenitor cells (RPC ) can give rise to all retinal cell types
bHLH transcription factor ATOG7(Math5) essential for establishing RGC fate.
RGC= retinal Ganglion Cells, earliest type to differentiate,
Atoh7-expressing subpopulation of RPC commits to an RGC fate.
Transcriptional regulator
Ebf3This gene encodes a member of the early B-cell
factor (EBF) family of DNA binding transcription factors. EBF proteins
are involved in B-cell differentiation, bone development and
neurogenesis, and may also function as tumor suppressors. The encoded
protein inhibits cell survival through the regulation of genes involved
in cell cycle arrest and apoptosis, and aberrant methylation or deletion
of this gene may play a role in multiple malignancies including
glioblastoma multiforme and gastric carcinoma. [provided by RefSeq, Sep
2011]GeneCards Summary for EBF3 GeneEBF3 (EBF Transcription Factor 3) is a Protein Coding gene.
Diseases associated with EBF3 include Hypotonia, Ataxia, And Delayed Development Syndrome and Neurogenic Bladder.
Among its related pathways are Differentiation of white and brown adipocyte.
Gene Ontology (GO) annotations related to this gene include protein dimerization activity.
An important paralog of this gene is EBF1.UniProtKB/Swiss-Prot Summary for EBF3 Gene Transcriptional activator (PubMed:28017373, 28017372, 28017370). Recognizes variations of the palindromic sequence 5'-ATTCCCNNGGGAATT-3' (By similarity).
(
COE3_HUMAN,Q9H4W6 )
EYA2, eyes absent homolog 2, early target gene of ATOH7, RGC specification. Functions both as protein phosphatase and as transcriptional coactivator
for SIX1, and probably also for SIX2, SIX4 and SIX5 (PubMed:12500905, 23435380).
Tyrosine phosphatase that dephosphorylates 'Tyr-142' of histone H2AX
(H2AXY142ph) and promotes efficient DNA repair via the recruitment of
DNA repair complexes containing MDC1. 'Tyr-142' phosphorylation of
histone H2AX plays a central role in DNA repair and acts as a mark that
distinguishes between apoptotic and repair responses to genotoxic stress
(PubMed:19351884).
Its function as histone phosphatase may contribute to its function in
transcription regulation during organogenesis. Plays an important role
in hypaxial muscle development together with SIX1 and DACH2; in this it
is functionally redundant with EYA1
Pax6-Atoh7-Eya2
pathway
Differentiation
factor Pou4f2 (Brain-Specific Homeobox/POU Domain Protein 3BThe protein encoded by this gene is a member of the POU-domain
transcription factor family and may be involved in maintaining visual
system neurons in the retina. The level of the encoded protein is also
elevated in a majority of breast cancers, resulting in accelerated tumor
growth. [provided by RefSeq, Sep 2011] Tissue-specific DNA-binding transcription factor involved in the development and differentiation of target cells (PubMed:19266028, 23805044).
Functions either as activator or repressor modulating the rate of
target gene transcription through RNA polymerase II enzyme in a
promoter-dependent manner (PubMed:19266028, 23805044).
Binds to the consensus octamer motif 5'-AT[A/T]A[T/A]T[A/T]A-3' of
promoter of target genes. Plays a fundamental role in the gene
regulatory network essential for retinal ganglion cell (RGC)
differentiation. Binds to an octamer site to form a ternary complex with
ISL1; cooperates positively with ISL1 and ISL2 to potentiate
transcriptional activation of RGC target genes being involved in RGC
fate commitment in the developing retina and RGC axon formation and
pathfinding. Inhibits DLX1 and DLX2 transcriptional activities
preventing DLX1- and DLX2-mediated ability to promote amacrine cell fate
specification. In cooperation with TP53 potentiates transcriptional
activation of BAX promoter activity increasing neuronal cell apoptosis.
Negatively regulates BAX promoter activity in the absence of TP53. Acts
as a transcriptional coactivator via its interaction with the
transcription factor ESR1 by enhancing its effect on estrogen response
element (ERE)-containing promoter. Antagonizes the transcriptional
stimulatory activity of POU4F1 by preventing its binding to an octamer
motif. Involved in TNFSF11-mediated terminal osteoclast differentiation
(By similarity).
(
PO4F2_HUMAN,Q12837 )https://www.genecards.org/cgi-bin/carddisp.pl?gene=POU4F2&keywords=Pou4f2
Abstract
The bHLH transcription factor ATOH7 (Math5) is essential for
establishing retinal ganglion cell (RGC) fate. However, Atoh7-expressing
retinal progenitor cells (RPCs) can give rise to all retinal cell
types, suggesting that other factors are involved in specifying RGCs.
The basis by which a subpopulation of Atoh7-expressing RPCscommits to
an RGC fate remains uncertain but is of critical importance to retinal
development since RGCs are the earliest cell type to differentiate.
To
better understand the regulatory mechanisms leading to cell-fate
specification, a binary genetic system was generated to specifically
label Atoh7-expressing cells with green fluorescent protein (GFP).
Fluorescence-activated cell sorting (FACS)-purified GFP(+) and GFP(-)
cells were profiled by RNA-seq. Here, we identify 1497 transcripts that
were differentially expressed between the two RPC populations.
Pathway
analysis revealed diminished growth factor signaling in Atoh7-expressing
RPCs, indicating that these cells had exited the cell cycle. In
contrast, axon guidance signals were enriched, suggesting that axons of
Atoh7-expressing RPCs were already making synaptic connections. Notably,
many genes enriched in Atoh7-expressing RPCs encoded transcriptional
regulators, and several were direct targets of ATOH7, including, and
unexpectedly, Ebf3 and Eya2.
We present evidence for a Pax6-Atoh7-Eya2
pathway that acts downstream of Atoh7 but upstream of differentiation
factor Pou4f2.
EYA2 is a protein phosphatase involved in protein-protein
interactions and posttranslational regulation. These properties, along
with Eya2 as an early target gene of ATOH7, suggest that EYA2 functions
in RGC specification. Our results expand current knowledge of the
regulatory networks operating in Atoh7-expressing RPCs and offer new
directions for exploring the earliest aspects of retinogenesis.
Transcription Factor ATOH734 Protein Atonal Homolog 734
This intronless gene encodes a member of the basic helix-loop-helix
family of transcription factors, with similarity to Drosophila atonal
gene that controls photoreceptor development. Studies in mice suggest
that this gene plays a central role in retinal ganglion cell and optic
nerve formation. Mutations in this gene are associated with nonsyndromic
congenital retinal nonattachment. [provided by RefSeq, Dec 2011].
Transcription factor that binds to DNA at the consensus sequence 5'-CAG[GC]TG-3' (PubMed:31696227). Dimerization with TCF3 isoform E47 may be required in certain situations (PubMed:31696227).
Binds to gene promoters and enhancer elements, and thereby regulates a
transcriptional program of retinal ganglion cell (RGC) determinant genes
(By similarity). Although the exact mechanism is not certain, retinal
transcription regulation by ATOH7 has a role in RGC determination and
survival, photoreceptor population development, targeting of RGC axons
to theoptic nerve and development of the retino-hypothalamic tract (By
similarity). Binds to its own promoter and enhancer sequences,
suggesting autoregulation of ATOH7 transcription (By similarity).
Required for retinal circadian rhythm photoentrainment (By similarity).
Plays a role in brainstem auditory signaling and binaural processing (By
similarity).
(
ATOH7_HUMAN,Q8N100 )-
STRING Interaction Network Preview (showing top 5 STRING interactants - click image to see top 25) TCF3 [ENSP00000262965] Transcription factor E2-alpha;
Transcriptional regulator. Involved in the initiation of neuronal
differentiation. Heterodimers between TCF3 and tissue- specific basic
helix-loop-helix (bHLH) proteins play major roles in determining
tissue-specific cell fate during embryogenesis, like muscle or early
B-cell differentiation. Dimers bind DNA on E- box motifs: 5'-CANNTG-3'.
Binds to the kappa-E2 site in the kappa immunoglobulin gene enhancer.
Binds to IEB1 and IEB2, which are short DNA sequences in the insulin
gene transcription control region
TCF4[ENSP00000381382] Transcription
factor 4; Transcription factor that binds to the immunoglobulin
enchancer Mu-E5/KE5-motif. Involved in the initiation of neuronal
differentiation. Activates transcription by binding to the E box
(5'-CANNTG-3'). Binds to the E-box present in the somatostatin receptor 2
initiator element (SSTR2-INR) to activate transcription (By
similarity). Preferentially binds to either 5'-ACANNTGT-3' or
5'-CCANNTGG-3'; Basic helix-loop-helix proteins Transcription factor 12; Transcriptional regulator. Involved in the
initiation of neuronal differentiation. Activates transcription by
binding to the E box (5'-CANNTG-3'); Basic helix-loop-helix proteins Identifier: ENSP00000388940, TCF12
TCF3 This gene encodes a member of the E protein (class I) family of
helix-loop-helix transcription factors. E proteins activate
transcription by binding to regulatory E-box sequences on target genes
as heterodimers or homodimers, and are inhibited by heterodimerization
with inhibitor of DNA-binding (class IV) helix-loop-helix proteins. E
proteins play a critical role in lymphopoiesis, and the encoded protein
is required for B and T lymphocyte development. Deletion of this gene or
diminished activity of the encoded protein may play a role in lymphoid
malignancies. This gene is also involved in several chromosomal
translocations that are associated with lymphoid malignancies including
pre-B-cell acute lymphoblastic leukemia (t(1;19), with PBX1), childhood
leukemia (t(19;19), with TFPT) and acute leukemia (t(12;19), with
ZNF384). Alternatively spliced transcript variants encoding multiple
isoforms have been observed for this gene, and a pseudogene of this gene
is located on the short arm of chromosome 9. [provided by RefSeq, Sep
2011]
Transcriptional regulator involved in the initiation of neuronal
differentiation and mesenchymal to epithelial transition(By
similarity). Heterodimers between TCF3 and tissue-specific basic
helix-loop-helix (bHLH) proteins play major roles in determining
tissue-specific cell fate during embryogenesis, like muscle or early
B-cell differentiation (By similarity). Together with TCF15, required
for the mesenchymal to epithelial transition (By similarity). Dimers
bind DNA on E-box motifs: 5'-CANNTG-3' (By similarity). Binds to the
kappa-E2 site in the kappa immunoglobulin gene enhancer (PubMed:2493990). Binds to IEB1 and IEB2, which are short DNA sequences in the insulin gene transcription control region (By similarity).
(
TFE2_HUMAN,P15923 )
[Isoform E47]: Facilitates ATOH7 binding to DNA at the consensus
sequence 5'-CAGGTG-3', and positively regulates transcriptional
activity.
(
TFE2_HUMAN,P15923 )
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