Genetics, Vol 127, 151-159, Copyright © 1991

INVESTIGATIONS

Four Distinct Regulatory Regions of the cut Locus and Their Effect on Cell Type Specification in Drosophila

S. Liu, E. McLeod and J. Jack
Molecular Biology Program, Sloan-Kettering Institute and Cornell University Graduate School of Medical Sciences, New York, New York 10021

The cut gene in Drosophila is necessary in at least one cell type, the external sensory organs, for proper cell type specification and morphogenesis. It is also expressed in a variety of other tissues, where its function is less well characterized. Previous work has demonstrated that mutations affecting all the tissues map in the transcribed and translated portion of the gene, while mutations that are tissue specific in their effects map in the 140 kb upstream of the most 5' exon known. Within that 140 kb, the mutations fall into four subregions, two of which contain mutations affecting unique sets of tissues and the other two of which contain mutations that affect a third set. Our examination of the defects of mutants, their complementation behavior, and their effect on the distribution of the cut protein in embryos, alters the picture in three important ways. First, some mutations convert the cells of the Malpighian tubules into what appear to be gut cells, suggesting that cut is necessary for cell type specification and morphogenesis in a variety of tissues. Second, mutations in each of the four subregions in the 140 kb of upstream DNA cause a different set of phenotypes, suggesting that the regulatory region contains at least four separate units with different tissue specific functions. And third, mutations have now been identified that map in the transcribed and translated portion of the gene but that have tissue specific effects.

This article has been cited by other articles:

				C. Cadieux, R. Harada, M. Paquet, O. Cote, M. Trudel, A. Nepveu, and M. Bouchard Polycystic Kidneys Caused by Sustained Expression of Cux1 Isoform p75 J. Biol. Chem., May 16, 2008; 283(20): 13817 - 13824. [Abstract] [Full Text] [PDF]

				E. Hatton-Ellis, C. Ainsworth, Y. Sushama, S. Wan, K. VijayRaghavan, and H. Skaer From the Cover: Genetic regulation of patterned tubular branching in Drosophila PNAS, January 2, 2007; 104(1): 169 - 174. [Abstract] [Full Text] [PDF]

				H. Seto, Y. Hayashi, E. Kwon, O. Taguchi, and M. Yamaguchi Antagonistic regulation of the Drosophila PCNA gene promoter by DREF and Cut. Genes Cells, May 1, 2006; 11(5): 499 - 512. [Abstract] [Full Text] [PDF]

				L. Sansregret, B. Goulet, R. Harada, B. Wilson, L. Leduy, J. Bertoglio, and A. Nepveu The p110 Isoform of the CDP/Cux Transcription Factor Accelerates Entry into S Phase. Mol. Cell. Biol., March 1, 2006; 26(6): 2441 - 2455. [Abstract] [Full Text] [PDF]

				J. J. Krupp, L. E. Yaich, R. J. Wessells, and R. Bodmer Identification of Genetic Loci That Interact With cut During Drosophila Wing-Margin Development Genetics, August 1, 2005; 170(4): 1775 - 1795. [Abstract] [Full Text] [PDF]

				M. Truscott, L. Raynal, Y. Wang, G. Berube, L. Leduy, and A. Nepveu The N-terminal Region of the CCAAT Displacement Protein (CDP)/Cux Transcription Factor Functions as an Autoinhibitory Domain that Modulates DNA Binding J. Biol. Chem., November 26, 2004; 279(48): 49787 - 49794. [Abstract] [Full Text] [PDF]

				Q. Zhu, U. Maitra, D. Johnston, M. Lozano, and J. P. Dudley The Homeodomain Protein CDP Regulates Mammary-Specific Gene Transcription and Tumorigenesis Mol. Cell. Biol., June 1, 2004; 24(11): 4810 - 4823. [Abstract] [Full Text] [PDF]

				M. Truscott, L. Raynal, P. Premdas, B. Goulet, L. Leduy, G. Berube, and A. Nepveu CDP/Cux Stimulates Transcription from the DNA Polymerase {alpha} Gene Promoter Mol. Cell. Biol., April 15, 2003; 23(8): 3013 - 3028. [Abstract] [Full Text] [PDF]

				B. Goulet, P. Watson, M. Poirier, L. Leduy, G. Berube, S. Meterissian, P. Jolicoeur, and A. Nepveu Characterization of a Tissue-specific CDP/Cux Isoform, p75, Activated in Breast Tumor Cells Cancer Res., November 15, 2002; 62(22): 6625 - 6633. [Abstract] [Full Text] [PDF]

				M. Santaguida, Q. Ding, G. Berube, M. Truscott, P. Whyte, and A. Nepveu Phosphorylation of the CCAAT Displacement Protein (CDP)/Cux Transcription Factor by Cyclin A-Cdk1 Modulates Its DNA Binding Activity in G2 J. Biol. Chem., November 30, 2001; 276(49): 45780 - 45790. [Abstract] [Full Text] [PDF]

				N. S. Moon, P. Premdas, M. Truscott, L. Leduy, G. Berube, and A. Nepveu S Phase-Specific Proteolytic Cleavage Is Required To Activate Stable DNA Binding by the CDP/Cut Homeodomain Protein Mol. Cell. Biol., September 15, 2001; 21(18): 6332 - 6345. [Abstract] [Full Text] [PDF]

				Z. Wang, A. Goldstein, R.-T. Zong, D. Lin, E. J. Neufeld, R. H. Scheuermann, and P. W. Tucker Cux/CDP Homeoprotein Is a Component of NF-µNR and Represses the Immunoglobulin Heavy Chain Intronic Enhancer by Antagonizing the Bright Transcription Activator Mol. Cell. Biol., January 1, 1999; 19(1): 284 - 295. [Abstract] [Full Text] [PDF]

				B. H. Judd Genes and Chromomeres: A Puzzle in Three Dimensions Genetics, September 1, 1998; 150(1): 1 - 9. [Full Text] [PDF]

				L. A. Johnston, B. D. Ostrow, C. Jasoni, and K. Blochlinger The Homeobox Gene cut Interacts Genetically With the Homeotic Genes proboscipedia and Antennapedia Genetics, May 1, 1998; 149(1): 131 - 142. [Abstract] [Full Text] [PDF]

				O. Coqueret, N. Martin, G. Berube, M. Rabbat, D. W. Litchfield, and A. Nepveu DNA Binding by Cut Homeodomain Proteins Is Down-modulated by Casein Kinase II J. Biol. Chem., January 30, 1998; 273(5): 2561 - 2566. [Abstract] [Full Text] [PDF]

				S. Jackson and K Blochlinger cut interacts with Notch and protein kinase A to regulate egg chamber formation and to maintain germline cyst integrity during Drosophila oogenesis Development, January 9, 1997; 124(18): 3663 - 3672. [Abstract] [PDF]

				O. Coqueret, G. Berube, and A. Nepveu DNA Binding by Cut Homeodomain Proteins Is Down-modulated by Protein Kinase C J. Biol. Chem., October 4, 1996; 271(40): 24862 - 24868. [Abstract] [Full Text] [PDF]

				S. E. Quaggin, G. B.V. Heuvel, K. Golden, R. Bodmer, and P. Igarashi Primary Structure, Neural-specific Expression, and Chromosomal Localization of Cux-2, a Second Murine Homeobox Gene Related to Drosophila cut J. Biol. Chem., September 13, 1996; 271(37): 22624 - 22634. [Abstract] [Full Text] [PDF]

				P. M. J. Lievens, J. J. Donady, C. Tufarelli, and E. J. Neufeld Repressor Activity of CCAAT Displacement Protein in HL-60 Myeloid Leukemia Cells J. Biol. Chem., May 26, 1995; 270(21): 12745 - 12750. [Abstract] [Full Text] [PDF]

				M Vervoort, D Zink, N Pujol, K Victoir, N Dumont, A Ghysen, and C Dambly-Chaudiere Genetic determinants of sense organ identity in Drosophila: regulatory interactions between cut and poxn Development, January 9, 1995; 121(9): 3111 - 3120. [Abstract] [PDF]

				V Andres, M D Chiara, and V Mahdavi A new bipartite DNA-binding domain: cooperative interaction between the cut repeat and homeo domain of the cut homeo proteins. Genes & Dev., January 15, 1994; 8(2): 245 - 257. [Abstract] [PDF]

				D A Harrison, D A Gdula, R S Coyne, and V G Corces A leucine zipper domain of the suppressor of Hairy-wing protein mediates its repressive effect on enhancer function. Genes & Dev., October 1, 1993; 7(10): 1966 - 1978. [Abstract] [PDF]

				K Blochlinger, L. Jan, and Y. Jan Postembryonic patterns of expression of cut, a locus regulating sensory organ identity in Drosophila Development, January 2, 1993; 117(2): 441 - 450. [Abstract] [PDF]

				K Blochlinger, L Y Jan, and Y N Jan Transformation of sensory organ identity by ectopic expression of Cut in Drosophila. Genes & Dev., July 1, 1991; 5(7): 1124 - 1135. [Abstract] [PDF]

				N. S. Moon, G. Berube, and A. Nepveu CCAAT Displacement Activity Involves CUT Repeats 1 and 2, Not the CUT Homeodomain J. Biol. Chem., September 29, 2000; 275(40): 31325 - 31334. [Abstract] [Full Text] [PDF]