國立高雄大學圖資館 |

Language: English

Back

Histone Regulation of the Maternal to Zygotic Transition: The Role of Histone Modifications on Zygotic Genome Activation /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Histone Regulation of the Maternal to Zygotic Transition: The Role of Histone Modifications on Zygotic Genome Activation /Maria De Jesus Benitez.
Author:	Benitez, Maria De Jesus,
Description:	1 electronic resource (88 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 86-01, Section: B.
Notes:	Advisors: Giraldez, Antonio J. Committee members: Greco, Valentina; Muzumdar, Mandar; Khokha, Mustafa.
Contained By:	Dissertations Abstracts International86-01B.
Subject:	Genetics.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30997417
ISBN:	9798383351598

Histone Regulation of the Maternal to Zygotic Transition: The Role of Histone Modifications on Zygotic Genome Activation /
Benitez, Maria De Jesus,

Histone Regulation of the Maternal to Zygotic Transition: The Role of Histone Modifications on Zygotic Genome Activation /Maria De Jesus Benitez. - 1 electronic resource (88 pages)

Source: Dissertations Abstracts International, Volume: 86-01, Section: B.

Following fertilization, the zebrafish embryo experiences significant reprogramming events to erase the inherited program of the terminally differentiated gametes, paving the way for the establishment of the zygotic program, which will drive the early steps of embryonic development. An essential step within this process is zygotic genome activation (ZGA), which refers to the time of development when the zygotic genome goes from being largely transcriptionally inactive to a gradual onset of transcriptional activity. In zebrafish, this process coincides with the deposition of many histone modifications associated with the positive regulation of transcription. Here, to explore the function of these transcription-associated marks during ZGA, I use a series of small-molecule inhibitors to screen against histone-modifying enzymes that cause gastrulation defects, as this tends to indicate defects in zygotic genome activation. I find that inhibitors against the acetyltransferases KAT2A and KAT8 tend to block gastrulation. Meanwhile, those against the H3K4 histone methyltransferase, KMT2, allow for the development of the embryo past gastrulation and do not prevent transcriptional appear to prevent transcriptional onset. While transcription is not globally downregulated, some transcripts are preferentially affected by the removal of the mark. Interestingly, inhibiting the eraser of H3K4me3, KDM5 blocks development at gastrulation. Given that this and other studies suggest that the activity of several epigenetic modifiers is essential for the correct regulation of Zygotic genome activation, I use the overexpression of lysine(K) to arginine(R) mutant histones in a histone-deficient background to interrogate the role of the histone modifications independent of any other enzymatic activity of the epigenetic modifier. In particular, to study the role of H3K27 in the onset of ZGA. Preventing the modification of the H3 tail blocks gastrulation and downregulated transcription in embryos injected with the mutant version of the histone. Interestingly, in mutants where only one lysine is replaced at a time, only K27R mutants mimic the developmental phenotype and the downregulation of transcription. All of these suggest a role for H3 lysine tail modifications in regulating ZGA and a critical role for K27.

English

ISBN: 9798383351598Subjects--Topical Terms:

189015
Genetics.
Subjects--Index Terms:

Zygotic genome activation

Histone Regulation of the Maternal to Zygotic Transition: The Role of Histone Modifications on Zygotic Genome Activation /
LDR:03864nmm a22004333i 4500 001 676286
005 20250420214335.5
006 m o d
007 cr|nu||||||||
008 250901s2024 miu||||||m |||||||eng d
020 $a 9798383351598
035 $a (MiAaPQD)AAI30997417
035 $a AAI30997417
040 $a MiAaPQD $b eng $c MiAaPQD $e rda
100 1 $a Benitez, Maria De Jesus, $e author. $3 990036
245 1 0 $a Histone Regulation of the Maternal to Zygotic Transition: The Role of Histone Modifications on Zygotic Genome Activation / $c Maria De Jesus Benitez.
264 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2024
300 $a 1 electronic resource (88 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Dissertations Abstracts International, Volume: 86-01, Section: B.
500 $a Advisors: Giraldez, Antonio J. Committee members: Greco, Valentina; Muzumdar, Mandar; Khokha, Mustafa.
502 $b Ph.D. $c Yale University $d 2024.
520 $a Following fertilization, the zebrafish embryo experiences significant reprogramming events to erase the inherited program of the terminally differentiated gametes, paving the way for the establishment of the zygotic program, which will drive the early steps of embryonic development. An essential step within this process is zygotic genome activation (ZGA), which refers to the time of development when the zygotic genome goes from being largely transcriptionally inactive to a gradual onset of transcriptional activity. In zebrafish, this process coincides with the deposition of many histone modifications associated with the positive regulation of transcription. Here, to explore the function of these transcription-associated marks during ZGA, I use a series of small-molecule inhibitors to screen against histone-modifying enzymes that cause gastrulation defects, as this tends to indicate defects in zygotic genome activation. I find that inhibitors against the acetyltransferases KAT2A and KAT8 tend to block gastrulation. Meanwhile, those against the H3K4 histone methyltransferase, KMT2, allow for the development of the embryo past gastrulation and do not prevent transcriptional appear to prevent transcriptional onset. While transcription is not globally downregulated, some transcripts are preferentially affected by the removal of the mark. Interestingly, inhibiting the eraser of H3K4me3, KDM5 blocks development at gastrulation. Given that this and other studies suggest that the activity of several epigenetic modifiers is essential for the correct regulation of Zygotic genome activation, I use the overexpression of lysine(K) to arginine(R) mutant histones in a histone-deficient background to interrogate the role of the histone modifications independent of any other enzymatic activity of the epigenetic modifier. In particular, to study the role of H3K27 in the onset of ZGA. Preventing the modification of the H3 tail blocks gastrulation and downregulated transcription in embryos injected with the mutant version of the histone. Interestingly, in mutants where only one lysine is replaced at a time, only K27R mutants mimic the developmental phenotype and the downregulation of transcription. All of these suggest a role for H3 lysine tail modifications in regulating ZGA and a critical role for K27.
546 $a English
590 $a School code: 0265
650 4 $a Genetics. $3 189015
650 4 $a Cellular biology. $3 708607
650 4 $a Biology. $3 188667
650 4 $a Molecular biology. $3 188737
653 $a Zygotic genome activation
653 $a Histone modifications
653 $a Embryonic development
653 $a Gastrulation
690 $a 0369
690 $a 0379
690 $a 0306
690 $a 0307
710 2 $a Yale University. $b Genetics. $e degree granting institution. $3 990037
720 1 $a Giraldez, Antonio J. $e degree supervisor.
773 0 $t Dissertations Abstracts International $g 86-01B.
790 $a 0265
791 $a Ph.D.
792 $a 2024
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30997417