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FLASH GENE

Symbol

TAL1

contributors: mct/npt/pgu - updated : 10-06-2016

HGNC name	T-cell acute lymphocytic leukemia 1
HGNC id	11556

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	TAL1 T-cell acute lymphocytic leukemia 1
Location	1p33      Physical location : 47.681.962 - 47.695.443
Synonym name	T-cell leukemia/lymphoma protein 5
	stem cell leukemia
	hematopoietic transcription factor
	T-cell leukemia/lymphoma protein 5
Synonym symbol(s)	SCL, TCL5, bHLHa17, SCL, TCL5, bHLHa17, tal-1

DNA

TYPE	functioning gene
STRUCTURE	16.08 kb     4 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	alternative promoter
	Binding site   enhancer
text structure	five separate enhancers during gene expression into the diverse subdomain of TAL1 expression

MAPPING

cloned

Y

linked

N

status

confirmed

Map	pter - STIL - TAL1 TAL1 - PDZK1IP1 - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003189 4 - 5018 NP_003180 34 331 - 2009 19497860 NM_001290406 3 - 4171 NP_001277335 - 172 - 2009 19497860 NM_001290403 5 - 4774 NP_001277332 - 331 - 2009 19497860 NM_001290404 6 - 4779 NP_001277333 - 331 - 2009 19497860 NM_001287347 5 - 4664 NP_001274276 - 331 - 2009 19497860 NM_001290405 - - 4647 NP_001277334 - 331 - 2009 19497860

EXPRESSION

Type

widely

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 Endocrine thyroid       highly Lymphoid/Immune thymus       highly Nervous brain midbrain         brain hindbrain         spinal cord         Reproductive female system uterus cervix   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Epithelial barrier/lining       Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic mature hematopoietic Cardiovascular endothelial cell

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	hematopoietic progenitors fetal liver

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

basic helix-loop-helix (HLH) domain

mono polymer

heteromer , dimer

HOMOLOGY

interspecies	ortholog to zebrafish tal1
	ortholog to murine Tal1

Homologene

FAMILY

basic helix-loop-helix (BHLH) family of transcription factor

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,chromatin/chromosome

basic FUNCTION	involved in the development of hemangioblats from early mesoderm, expressed in stem cells and absolutely required, in association with LMO2, in the generation of cell hematopoietic lineages
	having major functions during embryonic hematopoiesis and in adult erythropoiesis and megakaryocytopoiesis, a DNA-binding-dependent and -independent role in erythropoiesis
	may play an important role in hemopoietic differentiation, regulating immature human hematopoietic cell self-renewal and that this regulation requires TAL1 DNA-binding activity
	TAL1 transcription factor is essential for the development of the hematopoietic system and plays a role during definitive erythropoiesis in the adult
	novel role for GATA4 and TAL1 to affect skeletal myogenic differentiation and EPO response via cross-talk with SIRT1
	potential link between mechanisms driving TAL1 expression and increased EPO sensitivity in erythroid progenitor cells resulting in erythrocytosis
	has a unique mechanotransductive role in the cardiomyocyte
	likely has distinct roles in regulating the formation of endocardial intercellular junctions and maintaining endocardial identity
	is located in the up-stream of MEK/ERK pathway and partially regulates hematopoiesis by modulating the phosphorylation level of the key proteins in MEK/ERK pathway
	plays a critical role in chromatin loop formation between the gamma-globin genes and LCR, which is a critical step for the transcription of the gamma-globin genes
	is a central transcription factor for hematopoietic stem cell development in the embryo and for gene regulation during erythroid/megakaryocytic differentiation
	novel function of TAL1, RUNX1 and GATA1 in the transcriptional control of PRKACB activity, with implications for cellular signalling control during differentiation and disease

CELLULAR PROCESS	nucleotide, transcription
	cell organization/biogenesis

PHYSIOLOGICAL PROCESS

cardiovascular , development

text	vasculogenesis

PATHWAY

metabolism

signaling

a component	heterodimer with bHLH proteins
	forms heterodimers with TCF3
	part of the DNA-binding complex containing LMO2, LDB1, TAL1, and GATA1

INTERACTION

DNA	binding specifically to E-box motif

RNA

small molecule

protein	binds to DRG1
	binds to the LIM domain containing protein Rhombotin-2
	associates with many binding partners including E2A, GATA1, LMO2, LDB1, and ETO2, all of which are involved in modulating hematopoietic cell growth and differentiation
	TAL1 expression activated UBE2H expression, whereas TAL1 knock-down reduced UBE2H expression and ubiquitin transfer activity
	interacts with RUNX1 and ETS1, and these transcription factors are critically required for TAL1 binding to genes that modulate T-cell differentiation
	interacting with TRIM33 (regulation of adult hematopoiesis through TRIM33-mediated transcriptional repression of TAL1 and SPI1 target genes)
	interplay between PRKACA phosphorylation and TAL1-mediated epigenetic regulation that regulates hematopoietic transcription and differentiation programs during hematopoiesis and leukemogenesis
	GATA1 coregulators ZFPM1 and TAL1 dissociate from mitotic chromatin, suggesting that GATA1 functions as platform for their postmitotic recruitment
	forced TAL1 expression increases EPOR and erythropoietin hypersensitivity in erythroid progenitors
	TAL1 associates with GATA1, GATA2, lim-only protein LMO2, and LDB1 in a multimeric complex to regulate erythroid transcription
	TAL1 can recruit GATA1 and increase GATA1 binding to the EPOR promoter region to stimulate gene expression
	GATA1-dependent looping mechanisms may facilitate the conservation of TAL1 regulation despite cis-regulatory remodeling during vertebrate evolution
	GATA1 and TAL1 are bound to the regulatory regions of TFDP2 and upregulate its expression
	TAL1 interacts with the peptidylarginine deiminase IV (PADI4) and PADI4 acts as a coactivator of TAL1 by counteracting repressive histone arginine methylation
	KLF1 plays a role in facilitating and/or stabilizing GATA1 and TAL1 occupancy in the erythroid genes, contributing to the generation of active chromatin structure such as histone acetylation and chromatin looping
	in human hematopoietic stem/progenitor cells (HSPCs) DDIT4 is a direct TAL1 target gene
	link between TAL1 and the MTOR pathway in human early hematopoietic cells
	TAL1 together with hematopoietic transcription factors RUNX1 and GATA1 binds to the promoter of the isoform 3 of PRKACB

cell & other

REGULATION

activated by

activated and acetylated by EPB300/CREBBP, LMO1, LMO2, ICAF

ASSOCIATED DISORDERS

corresponding disease(s)

TAL1

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   translocation     translocation t(1;14) (p34,q11) or deletion in T cell acute lymphoblastic leukemia with worse response to treatment tumoral       gain of function Aberrant activation is involved in up to 60p100 of T cell acute lymphoblastic leukemia (T-ALL) cases, indicating that misregulation of TAL1's activity may lead to the development of T cell leukemia tumoral     --other   with LYL1, aberrantly over-expressed in leukemia as a result of chromosomal translocations tumoral     --low   by aberrant methylation of TAL1 in pediatric B-cell acute lymphoblastic leukemia (pMID: 25830127) tumoral       gain of function aberrant TAL1 activation is mediated by an interchromosomal interaction in human T-cell acute lymphoblastic leukemia

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS