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Analysis of genes involved in cell-specific control of programmed cell death in Caenorhabditis elegans

IP.com Disclosure Number: IPCOM000128048D
Original Publication Date: 1998-Dec-31
Included in the Prior Art Database: 2005-Sep-14
Document File: 7 page(s) / 23K

Publishing Venue

Software Patent Institute

Related People

Metzstein, Mark M: AUTHOR [+3]

Related Documents

http://theses.mit.edu:80/Dienst/UI/2.0/Describe/0018.mit.theses/1998-192: URL

Abstract

Programmed cell death is an important process regulating cell number in the development of all animals. Two genes, ces-1 and ces-2 control programmed cell death in a subset of developing neurons in C. elegans. To understand how ces-1 and ces-2 might act to regulate programmed cell death, we have cloned these genes. We find that both ces-1 and ces-2 encode transcription factors. By sequence and DNA-binding specificity CES-1 is a member of the Snail family of zinc-finger proteins, and most similar to the Drosophila protein Scratch. CES-2 is a bZIP protein closest in sequence and DNA-binding specificity to members of the vertebrate PAR subfamily. We have analyzed ces-1 regulation and, by conservation in the related nematode C. briggsae and by the position of the ces-1 gainof-function mutations, identified a putative control element 5' of ces-1 coding sequences. This element contains a site that can be bound by CES-2 protein, suggesting ces-1 may be transcriptionally regulated directly by ces-2. This element also contains five Snaillike binding sites, suggesting ces-1 may regulate its own transcription. These results suggest that programmed cell death, like many cell fates, is under transcriptional control, and that a transcriptional cascade control the deaths of at least some cells in C. elegans. We propose that some of the ced genes, which are involved in the execution of programmed cell death in C. elegans, are transcriptionally regulated by CES-1 and/or CES-2. Additionally, both ces-1 and ces-2 have homologues which might function in regulating programmed cell death in mammalian cells, suggesting the functions of ces-1 and ces-2 may be evolutionarily conserved. Supervisor: H. Robert Horvitz Professor of Biology MIT

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Analysis of genes involved in cell-specific control of programmed cell death in Caenorhabditis elegans

by

Mark M. Metzstein


B. A. Cambridge University, 1990 Submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY at the Massachusetts Institute of Technology February 1999
(c) 1998 Mark Metzstein. All rights reserved.

The author hereby grants MIT permission to reproduce and to distribute paper and electronic copies of this thesis document in whole or in part.

SIGNATURE OF author: [[signature omitted]]

Department of Biology September 30th 1998

CERTIFIED BY: [[SIGNATURE OMITTED]]
H. Robert Horvitz

Professor of Biology Thesis Supervisor ACCEPTED BY: [[SIGNATURE OMITTED]]

Alan Grossman Chairman of the Graduate Committee Department of Biology ARCHIVES MASSACHUSETTS INSTITUTE OF TECHNOLOGY LIBRARIES APR 01 1999

1

Massachusetts Institute of Technology Page 1 Dec 31, 1998

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Analysis of genes involved in cell-specific control of programmed cell death in Caenorhabditis elegans

Analysis of genes involved in cell-specific cont.-ol of programmed cell death in Caenorhabdit-is elegans

Mark M. Metzstein

ABSTRACT

Programmed cell death is an important process regulating cell number in the development of all animals. Two genes, ces-1 and ces-2 control programmed cell death in a subset of developing neurons in C. elegans.

To understand how ces-1 and ces-2 might act to regulate programmed cell death, we have cloned these genes. We find that both ces-1 and ces-2 encode transcription factors. By sequence and DNA-binding specificity CES-1 is a member of the Snail family of zinc-finger proteins, and most similar to the Drosophila protein Scratch. CES-2 is a bZIP protein closest in sequence and DNA-binding specificity to members of the vertebrate PAR subfamily.

We have analyzed ces-1 regulation and, by conservation in the related nematode C. briggsae and by the position of the ces-1 gainof-function mutations, identified a putative control element 5' of ces-1 coding sequences. This element contains a site that can be bound by CES-2 protein, suggesting ces-1 may be transcriptionally regulated directly by ces-2. This element also contains five Snaillike binding sites, suggesting ces-1 may regulate its own transcription.

These results suggest that programmed cell death, like many cell fates, is under transcriptional control, and that a transcriptional cascade control the deaths of at least some cells in C. elegans. We propose that some of the ced genes, which are involved in the execution of programmed cell death in C. elegans, are transcriptionally regulated by CES-1 and/or CES-2. Additionally, both ces-1 and ces-2 have homologues which might function in regul...