Disease relevance of NHLH1

• In the present study, we have identified LMO3 and HEN2, which encodes a neuronal basic helix-loop-helix protein, as genes whose expression levels were higher in unfavorable neuroblastomas compared with those of favorable tumors [1].
• Helix-loop-helix genes translocated in lymphoid leukemia [2].
• Background: In a previous study from our lab, adult males with non-syndromic cleft lip and/or palate (NSCLP) were shown to have significantly lower temporal lobe gray matter volume than matched controls [3].
• NSCL-1 expression was detected in all developing cranial ganglia including the petrosal and vestibulocochlear ganglion, in inner and outer hair cells of the organ of Corti and in hair cells of the vestibular system [4].
• The helix-loop-helix protein Id-2 enhances cell proliferation and binds to the retinoblastoma protein [5].

Psychiatry related information on NHLH1

• Inhibition of myeloid differentiation by the helix-loop-helix protein Id [6].

High impact information on NHLH1

• A partnership between the dioxin receptor and a basic helix-loop-helix protein [7].
• Furthermore, in fibroblasts expressing transfected beta-cell lmx-1, the addition of the Far-binding, basic helix-loop-helix protein shPan-1 (the hamster equivalent of human E47) causes a dramatic synergistic activation [8].
• Synergistic activation of the insulin gene by a LIM-homeo domain protein and a basic helix-loop-helix protein: building a functional insulin minienhancer complex [8].
• TFE3: a helix-loop-helix protein that activates transcription through the immunoglobulin enhancer muE3 motif [9].
• A key role in this feedback loop was attributed to the PAS domain helix-loop-helix protein CLOCK, on the basis of a dominant-negative mutation in this transcription factor [10].

Chemical compound and disease context of NHLH1

• Fusion of the NH2-terminal domain of the basic helix-loop-helix protein TCF12 to TEC in extraskeletal myxoid chondrosarcoma with translocation t(9;15)(q22;q21) [11].
• Helix-loop-helix Id (Inhibitor of DNA binding) proteins are distinct from bHLH transcription factors in that they lack the basic domain necessary for DNA binding [12].

Biological context of NHLH1

• In comparison with the ubiquitously expressed bHLH protein E47, HEN1 is a very modest transcriptional activator and titration experiments indicate that HEN1, like TAL1, represses E47 mediated transcriptional activation [13].
• HEN1 was cloned by virtue of its homology to TAL1, a bHLH protein important for early hematopoiesis [13].
• To characterize the transcriptional capacity of HEN1 alone or together with LMO2 and LMO4, we performed reporter gene assays [13].
• NSCL-1 is relatively G+C-rich (63%) in the sequences upstream of transcription initiation and has multiple potential binding sites for transcription factors that bind to G+C-rich sequences (e.g. AP-2) [14].
• The tal gene undergoes chromosome translocation in T cell leukemia and potentially encodes a helix-loop-helix protein [15].

Anatomical context of NHLH1

• Overexpression of HEN1 in hippocampal precursor cells resulted in neurite extension, which could be prevented by LMO4 [13].
• The LIM protein RBTN2 and the basic helix-loop-helix protein TAL1 are present in a complex in erythroid cells [16].
• NSCL-1 is expressed in a larger number of these cell lines [14].
• Studies of expression in normal tissues demonstrated expression of NSCL-1 and NSCL-2 in the developing central and peripheral nervous system, most likely in developing neurons [14].
• Cloning and characterization of a basic helix-loop-helix protein expressed in early mesoderm and the developing somites [17].

Associations of NHLH1 with chemical compounds

• Expression of the helix-loop-helix protein inhibitor of DNA binding-1 (ID-1) is activated by all-trans retinoic acid in normal human keratinocytes [18].
• Proneural Basic Helix-Loop-Helix Proteins and Epidermal Growth Factor Receptor Signaling Coordinately Regulate Cell Type Specification and cdk Inhibitor Expression during Development [19].
• Helix-loop-helix peptides as scaffolds for the construction of bridged metal assemblies in proteins: the spectroscopic A-cluster structure in carbon monoxide dehydrogenase [20].
• Molecular Architecture of the DNA-Binding Region and Its Relationship to Classification of Basic Helix-Loop-Helix Proteins [21].
• The new anthracycline analogue, 4'-iodo-4'-deoxydoxorubicin (I-DOX), was administered at 70 mg/m2 as first chemotherapy in 61 patients with advanced NSCL (19), colon (20) and breast cancers (22) [22].

Physical interactions of NHLH1

• By mammalian two-hybrid analysis, we show that HEN1 interacts with both LMO2 and LMO4 [13].

Other interactions of NHLH1

• The LIM-only protein LMO4 modulates the transcriptional activity of HEN1 [13].
• DroNHLH is 87% identical to NHLH1 and NHLH2 within the bHLH domain [23].
• Helix-loop-helix proteins LYL1 and E2a form heterodimeric complexes with distinctive DNA-binding properties in hematolymphoid cells [24].
• We identified a previously unreported transcript, designated BHLHB1 (for basic domain, helix-loop-helix protein, class B, 1) that had been activated by the translocation [25].
• These studies show that the bHLH domain of TAL1 selectively interacts with the bHLH domains of E12 and E47, but not with the Id1 helix-loop-helix protein [26].

Analytical, diagnostic and therapeutic context of NHLH1

• Methods: Manual tracing of the STP in NSCLP males and matched controls was performed on magnetic resonance imaging (MRI) scans [3].
• Examination of 12- and 13-day mouse embryos by in situ hybridization revealed expression of NSCL in the developing nervous system [27].
• We report here the molecular cloning and chromosomal localization of an additional member of the helix-loop-helix (HLH) family of transcription factors, NSCL [27].
• Gel mobility shift assays show that NSCL-1 only binds DNA as a heterodimeric complex with the ME1a E-protein [28].
• PURPOSE: To evaluate brain morphology of adult males with nonsyndromic clefts of the lip and/or palate (NSCLP) in comparison to a matched healthy control group [29].

References