Functional distinctness of closely related transcription factors: a comparison of the Atonal and Amos proneural factors.
Using the well-characterised paradigm of Drosophila sensory nervous system development, we examine the functional distinctness of the Amos and Atonal (Ato) proneural transcription factors, which have different mutant phenotypes but share very high similarity in their signature bHLH domains. Using misexpression and mutant rescue assays, we show that Ato and Amos proteins have abundantly distinct intrinsic proneural capabilities in much of the ectoderm. The eye, however, is an exception: here both proteins share the capability to direct the R8 photoreceptor fate choice. Therefore, functional distinctness between these closely related transcription factors vary with developmental context, indicating different molecular mechanisms of specificity in different contexts. Consistent with this, the structural basis for their distinctness also varies depending upon the function in question. In previous studies of neural bHLH factors, specificity invariably mapped to the bHLH domain sequence. Similarly, and despite their high similarity, much of the Amos' specificity relative to Ato maps to Amos-specific residues in its bHLH domain. For Ato-specific functions, however, the Amos bHLH domain can substitute for that of Ato. Consequently, Ato's specificity relative to Amos requires the non-bHLH portion of the Ato protein. Ato provides a powerful precedence for a role of non-bHLH sequences in modulating bHLH functional specificity. This has implications for structural and functional comparisons of other closely related transcription factors, and for understanding the molecular basis of specificity.
Maung
Sam M T W
SM
Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh EH8 9XD, UK.
Jarman
Andrew P
AP
D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000502:physiology; D018257:Helix-Loop-Helix Motifs / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D012903:Smell / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C405512:Amos protein, Drosophila; C082142:ato protein, Drosophila
Mol Cell Biol. 2000 Jan;20(2):429-40
10611221
Genes Cells. 1997 Mar;2(3):225-33
9189759
Neuron. 2000 Jan;25(1):69-78
10707973
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6815-9
10823908
Cell. 2000 Aug 4;102(3):349-62
10975525
Neuron. 2001 Feb;29(2):415-28
11239432
Dev Biol. 2002 Jul 1;247(1):137-48
12074558
Nat Rev Neurosci. 2002 Jul;3(7):517-30
12094208
Genetics. 2003 Apr;163(4):1403-12
12702684
Development. 2003 Oct;130(19):4683-93
12925594
Development. 2004 Mar;131(6):1319-30
14993186
Development. 2004 Apr;131(8):1679-89
15084454
Mol Cell Biol. 2004 Nov;24(21):9517-26
15485919
Biotechniques. 1990 May;8(5):528-35
2357375
EMBO J. 1990 Nov;9(11):3583-92
2120046
Int J Dev Biol. 1998 Mar;42(2):163-70
9551861
Mech Dev. 1998 Aug;76(1-2):117-25
9767145
Cell Mol Life Sci. 2005 Sep;62(18):2036-49
16003490
BMC Dev Biol. 2006;6:53
17094800
Dev Genes Evol. 2007 Mar;217(3):209-19
17260155
Genetics. 2002 Feb;160(2):623-35
11861566
Science. 1992 May 15;256(5059):1027-30
1317057
Trends Genet. 1992 Jun;8(6):202-8
1496555
Cell. 1993 Jul 2;73(7):1307-21
8324823
Cell. 1994 May 6;77(3):451-9
8181063
Nature. 1994 Jun 2;369(6479):398-400
8196767
Genes Dev. 1994 Apr 15;8(8):970-80
7926781
Development. 1995 Jul;121(7):2019-30
7635049
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13239-44
8917575
Neuron. 2000 Jan;25(1):57-67
10707972