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A Paradigm of Transcriptional Regulation in the C. elegans.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	A Paradigm of Transcriptional Regulation in the C. elegans./
Author:	Rabby, Md. Khoshnade.
Description:	1 online resource (156 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 85-06, Section: B.
Contained By:	Dissertations Abstracts International85-06B.
Subject:	Biology. -
Online resource:	click for full text (PQDT)
ISBN:	9798381163421

A Paradigm of Transcriptional Regulation in the C. elegans.
Rabby, Md. Khoshnade.

A Paradigm of Transcriptional Regulation in the C. elegans. - 1 online resource (156 pages)

Source: Dissertations Abstracts International, Volume: 85-06, Section: B.

Thesis (Ph.D.)--The Catholic University of America, 2024.

Includes bibliographical references

Multicellular animals originate from numerous cellular divisions in the developing zygote. These developmental divisions are well-coordinated and well-programmed to form different functional cells, tissues, and organs. Many factors, cofactors, and DNA elements play a vital role in the transcriptional regulation that leads to individual cellular identity. To ensure the best use of cellular resources and to keep cellular homeostasis, genes need to be turned on and off depending on cellular and environmental cues. Here, we discovered several developmental factors along with their DNA elements that participate in proper tissue-specific gene regulation in a paradigm of a transcriptional network. The first discovery is a homeobox domain transcription factor in the model nematode, C. elegans Homeobox-24 (CEH-24) and its binding motif CACTT that controls a developmental gene that expresses a signaling protein, Apex-related gene, arg-1. We discovered CEH-24's dual function as an activator and a repressor in different developmental periods. This transcription factor is predicted to bind to the CACTT site in the arg-1 promoter region to regulate arg-1 expression. Besides the activator role, we discovered its tissue-specific repressive role in controlling one of the lineage-specific basic helix-loop-helix (bHLH) transcription factors, HLH-8. Another exciting discovery was identifying a histone acetyltransferase, CBP/p300 homolog-1 (CBP-1), that also has a role in arg-1 gene regulation. The most exciting part of our discovery is the role of several intronic DNA elements that could influence gene expression by enhancing or repressing transcription. We identified one of the intronic elements, the E2 box in the hlh-8 intron1. Mutational studies of the E2 sequence in the transcription factor led to a loss of expression of the downstream target arg-1. The E2 element acts as an enhancer switch to activate arg-1 transcription. We also discovered another intronic element in intron 3 of the hlh-8 gene that appears to modulate the level of transcription through the influence of CEH-24. Upon mutation of this site, the enteric muscle brightness of the arg-1::gfp expression in adult animals intensified more than the wild-type enteric muscles. This tissue-specific effect leads to the hypothesis that this element may act as a time-dependent repressive switch for hlh-8 expression in enteric muscles. We propose this switch prevents the transcription of hlh-8 with the help of CEH-24. Finally, we isolated suppressor strains that alleviated one of the phenotypes of an HLH-8 mutant with an E29G amino acid substitution that is analogous to a human craniofacial patient allele. In the suppressed strains, the arg-1::gfp expression is restored in the VMs and may be due to a second-site mutation in a related gene. Though the specific genes were not identified yet, their identity is likely to add to the complexity of arg-1 transcription suggesting that this gene will continue to be a fruitful paradigm for understanding tissue-specific gene regulation.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9798381163421Subjects--Topical Terms:

599573
Biology.
Subjects--Index Terms:

Tissue-specific gene regulationIndex Terms--Genre/Form:

554714
Electronic books.

A Paradigm of Transcriptional Regulation in the C. elegans.
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