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The Transcriptional Regulation by MYSM1 in Hematopoietic Stem and Progenitor Cells.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The Transcriptional Regulation by MYSM1 in Hematopoietic Stem and Progenitor Cells./
作者:	Wang, HanChen.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
面頁冊數:	110 p.
附註:	Source: Masters Abstracts International, Volume: 82-10.
Contained By:	Masters Abstracts International82-10.
標題:	Protein synthesis. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28383907
ISBN:	9798708709219

The Transcriptional Regulation by MYSM1 in Hematopoietic Stem and Progenitor Cells.
Wang, HanChen.

The Transcriptional Regulation by MYSM1 in Hematopoietic Stem and Progenitor Cells. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 110 p.

Source: Masters Abstracts International, Volume: 82-10.

Thesis (M.Sc.)--McGill University (Canada), 2020.

This item must not be sold to any third party vendors.

Myb-like, Swirm and MPN domain-containing protein 1 (MYSM1) is a transcriptional regulator essential to the functions of hematopoietic stem cells (HSCs) in both human and mouse. Previous studies show that in Mysm1-/- mice, the p53-regulated stress-response is induced and leads to HSC dysfunction and depletion of downstream progenitors and mature blood cells. In Mysm1-/-p53-/- mice, these phenotypes revert to normal, indicating an antagonistic role of MYSM1 to p53. It is established that the HSC dysfunction in Mysm1-deficiency is driven by p53. However, the mechanism leading to p53 activation in Mysm1-deficiency remains unknown. In this study, we present the first data set describing the transcriptomic alterations in Mysm1-/- mouse HSCs and multipotent progenitors (MPPs) using RNA-Seq and the genome-wide binding pattern of MYSM1 in mouse hematopoietic progenitor cell lines using ChIP-Seq. I analyzed and identified profound changes in the transcriptome of Mysm1-deficient mice, including a group of downregulated translation-related and ribosomal protein-encoding genes (RP-genes). I showed that MYSM1 binds to the promoters of these genes and orchestrates the induction of transcriptional activation marker H3K27ac, suggesting directly regulation of these genes by MYSM1. I validated these findings use ChIP-qPCR. Furthermore, I showed that the expressions of the RP-genes are independent of p53 activation in Mysm1-deficiency and examined the roles of transcriptional regulators PRC1 and c-MYC in regulating RP-gene expressions. Overall, this work provides insight into the transcriptional control by MYSM1 in hematopoietic stem and progenitor cells and advances our knowledge of bone marrow failure in human Mysm1-deficiency.

ISBN: 9798708709219Subjects--Topical Terms:

3681687
Protein synthesis.
Subjects--Index Terms:

MYSM1

The Transcriptional Regulation by MYSM1 in Hematopoietic Stem and Progenitor Cells.
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245 1 4 $a The Transcriptional Regulation by MYSM1 in Hematopoietic Stem and Progenitor Cells.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2020
300 $a 110 p.
500 $a Source: Masters Abstracts International, Volume: 82-10.
500 $a Advisor: Nijnik, Anastasia;Langlais, David.
502 $a Thesis (M.Sc.)--McGill University (Canada), 2020.
506 $a This item must not be sold to any third party vendors.
520 $a Myb-like, Swirm and MPN domain-containing protein 1 (MYSM1) is a transcriptional regulator essential to the functions of hematopoietic stem cells (HSCs) in both human and mouse. Previous studies show that in Mysm1-/- mice, the p53-regulated stress-response is induced and leads to HSC dysfunction and depletion of downstream progenitors and mature blood cells. In Mysm1-/-p53-/- mice, these phenotypes revert to normal, indicating an antagonistic role of MYSM1 to p53. It is established that the HSC dysfunction in Mysm1-deficiency is driven by p53. However, the mechanism leading to p53 activation in Mysm1-deficiency remains unknown. In this study, we present the first data set describing the transcriptomic alterations in Mysm1-/- mouse HSCs and multipotent progenitors (MPPs) using RNA-Seq and the genome-wide binding pattern of MYSM1 in mouse hematopoietic progenitor cell lines using ChIP-Seq. I analyzed and identified profound changes in the transcriptome of Mysm1-deficient mice, including a group of downregulated translation-related and ribosomal protein-encoding genes (RP-genes). I showed that MYSM1 binds to the promoters of these genes and orchestrates the induction of transcriptional activation marker H3K27ac, suggesting directly regulation of these genes by MYSM1. I validated these findings use ChIP-qPCR. Furthermore, I showed that the expressions of the RP-genes are independent of p53 activation in Mysm1-deficiency and examined the roles of transcriptional regulators PRC1 and c-MYC in regulating RP-gene expressions. Overall, this work provides insight into the transcriptional control by MYSM1 in hematopoietic stem and progenitor cells and advances our knowledge of bone marrow failure in human Mysm1-deficiency.
520 $a La proteine MYSM1 (Myb-like, Swirm and MPN domain-containing protein 1) est un regulateur transcriptionnel essentiel aux fonctions des cellules souches hematopoietiques (CSH), autant chez l'homme que chez la souris. Des etudes anterieures ont demontre que chez les souris Mysm1-/-, l'absence de MYSM1 induit une reponse au stress regulee par p53, menant a une dysfonction des CSH, a l'epuisement des cellules progenitrices qui se retrouvent en aval des CSH, et a une depletion des cellules sanguines matures. Chez les souris Mysm1-/-p53-/-, ces phenotypes reviennent a la normale, signalant que MYSM1 agit en antagoniste vis-a-vis p53. Il est deja bien etabli que dans le contexte d'une deficience en Mysm1, les dysfonctions observees aupres des CSH sont provoquees par p53. Cependant, le mecanisme precis conduisant a l'activation de p53 en l'absence de Mysm1 demeure inconnu. Nous presentons dans cette etude un premier ensemble de donnees qui revele a l'aide du sequencage de l'ARN les alterations transcriptomiques des CSH et des cellules progenitrices multipotentes (MPP) issues de souris Mysm1-/-. De plus, cet ensemble de donnees nous a permis de noter les positions genomiques precises ou peuvent se lier la proteine MYSM1 a l'echelle du genome de la souris, a partir de lignees de cellules progenitrices hematopoietiques soumises a la methode ChIP-Seq. En ayant effectue ces analyses, j'ai identifie d'importants changements dans le transcriptome des souris deficientes en Mysm1, notamment l'expression reduite d'une famille de genes qui encode diverses sous-unites de proteines liees a la traduction et au ribosome (genes RP). J'ai demontre que MYSM1 se lie aux promoteurs de ces genes RP pour ensuite induire le marqueur d'activation transcriptionnelle H3K27ac, ce qui suggere que MYSM contribue a la regulation de ces genes de facon directe. J'ai valide ces resultats en utilisant la methode ChIP-qPCR. De plus, j'ai decouvert que l'expression des genes RP est independante de l'activation de p53 dans le contexte d'une deficience en Mysm1, et j'ai examine le role des regulateurs transcriptionnels PRC1 et c-MYC dans le controle de l'expression des genes RP. Globalement, ce travail nous permet de mieux comprendre l'important role de MYSM1 dans la regulation transcriptionnelle des cellules souches, des cellules progenitrices hematopoietiques, et de l'insuffisance de la moelle osseuse observee en cas de deficience humaine en MYSM1.
590 $a School code: 0781.
650 4 $a Protein synthesis. $3 3681687
650 4 $a Gene expression. $3 643979
650 4 $a Flow cytometry. $3 600581
650 4 $a Metabolism. $3 541349
650 4 $a Stem cells. $3 767761
650 4 $a Biosynthesis. $3 516407
650 4 $a Proteins. $3 558769
653 $a MYSM1
653 $a Hematopoietic stem cells
653 $a Progenitor cells
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710 2 $a McGill University (Canada). $3 1018122
773 0 $t Masters Abstracts International $g 82-10.
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791 $a M.Sc.
792 $a 2020
793 $a English
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