The Significance of the Intrinsically Disordered Regions for the Functions of the bHLH Transcription Factors
Abstract
:1. Introduction
2. The Role of the bHLH Proteins in Transcription
3. The bHLH Transcription Factors as IDPs
4. The Role of IDPs in Maintaining/Creation of LLPS
5. The Transcription Regulation and LLPS
6. Concluding Remarks and Future Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AHR | Aryl hydrocarbon receptor |
AS-C | Achaete scute complex |
ARNT | Aryl hydrocarbon receptor nuclear translocator |
bHLH | Helix–loop–helix |
ccRCC | Clear cell renal cell carcinoma |
CLOCK | Circadian locomotor output cycles protein kaput |
CTD | C-terminal domain |
CycT1 | Cyclin T1 |
EMC | Extramacrochaetae |
E(spI) | Enhancer of split |
ER | Estrogen receptor |
ESC | Embryonic stem cells |
GCE | Germ cell-expressed protein |
GRO | Groucho |
HAT | Histone transacetylase |
HIF | Hypoxia-inducible factor |
HSCa | Hematopoietic stem cells |
HRD | histidine reach domain |
ID | Inhibitor of DNA binding |
IDPs | Intrinsically disordered proteins |
IDRs | Intrinsically disordered regions |
LLPS | liquid-liquid phase separation |
LZ | Leucine zipper motif |
MET | Methoprene-tolerant protein |
MXI1 | Max interacting protein |
Ngn2 | Neurogenin |
NPAS | Neuronal PAS domain-containing protein |
PAS | Period-arylhydrocarbon nuclear translocator-single minded domain |
Pol II | RNA polymerase II |
SE | Super-enhancer |
SIM | Single-minded protein |
SIMA | Similar protein |
S/MARs | Scaffold/matrix associate regions |
SREBP | Sterol-responsive element-binding protein |
TAD | Transactivation domain |
TAZ | Tafazzin |
TFs | Transcription factors |
TRH | Trachealess protein |
USF | Upstream stimulatory factor |
VHL | Von Hippel-Lindau tumor suppressor |
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Structural Motif Dimerization | Representative Members | Short Description |
---|---|---|
class I (E proteins)/ group A | ||
bHLH, homo- and heterodimerization | Vertebrate: E12, E47 [17], HEB [18,19], TCF4 [20] Invertebrate: Daughterless | transcription activators, ubiquitous expression, neurogenesis, immune cell development, sex development, gonadogenesis |
class II/ group A | ||
bHLH, preferred heterodimerization with class I partners | Vertebrate: MYOD, Myogenin, MYF5-6, Ngn1-3, ATOH, NeuroD, NDRF, MATH, MASH, ASCL1 [21], TAL1/SCL [22], OLIG1-3 [23] Invertebrate: TWIST [24], AS-C | transcription activators, tissue specific expression, muscle development, neuro-genesis, generation of autonomic and olfactory neurons, development of granule neurons and external germinal layer of cerebellum, oligodendrocyte development, specification of blood lineage and maturation of several hematopoietic cells, pancreatic development |
class III/ group B | ||
bHLH-LZ | Vertebrate: MYC [25], USF, TFE3, SREBP1-2 Drosophila: MYC Plants: MYC2 | transcription activators/represors, oncogenic transformation, apoptosis, cellular differentiation, proliferation, cholesterol-mediated induction of the low-density lipoprotein receptor, jasmonate signaling (plants) |
class IV/ group B | ||
bHLH, heterodimerisation with each other and MYC proteins | Vertabrate: MAD, MAX [26], MXI1 Drosophila: MNT, MAX | transcription regulators lacking transactivation domain (TAD) |
class V/ group D | ||
HLH (no basic region) | Vertebrate: ID1-4 [27] Invertebrate:EMC | negative transcription regulators of class I and II (group A) proteins, no DNA binding, regulation by sequestration. |
class VI/ group B | ||
bHLH-O, (presence of proline in basic region) | Vertebrate: HES, HEY1-3 [28], STRA13, HERP1-2 [29] Drosophila: HAIRY [30], E(spI) | negative transcription regulators interacting with corepressors (Groucho); neurogenesis, vasculogenesis, mesoderm segmentation, myogenesis, T lymphocyte development, cardiovascular development and homeostasis; effectors of Notch signalling [28]; in Drosophila: regulation of differentiation, anteroposterior segmentation and sex determination |
class VII/ group C - subclass I | ||
bHLH-PAS, heterodimerization with subclass II | Vertebrate: AHR [31], HIF1-3α [32], SIM1-2 [33], CLOCK [34], NPAS1-4 [35,36,37,38,39] Drosophila: MET [40], GCE, SIMA, TRH | transcription regulation in response to physiological and environmental signals: xenobiotics, hypoxia, development, circadian rhytms |
class VII/ group C - subclass II | ||
bHLH-PAS, homo- and heterodimerization with subclass I | Vertebrate: ARNT [41], ARNT2, BMAL1, BMAL2 Drosophila: TANGO, CYCLE | general partners for subclass I bHLH-PAS proteins |
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Tarczewska, A.; Greb-Markiewicz, B. The Significance of the Intrinsically Disordered Regions for the Functions of the bHLH Transcription Factors. Int. J. Mol. Sci. 2019, 20, 5306. https://doi.org/10.3390/ijms20215306
Tarczewska A, Greb-Markiewicz B. The Significance of the Intrinsically Disordered Regions for the Functions of the bHLH Transcription Factors. International Journal of Molecular Sciences. 2019; 20(21):5306. https://doi.org/10.3390/ijms20215306
Chicago/Turabian StyleTarczewska, Aneta, and Beata Greb-Markiewicz. 2019. "The Significance of the Intrinsically Disordered Regions for the Functions of the bHLH Transcription Factors" International Journal of Molecular Sciences 20, no. 21: 5306. https://doi.org/10.3390/ijms20215306