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Histone H1 and Chromosomal Protein H...

Schauwecker, Suzanne Marie.

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Histone H1 and Chromosomal Protein HMGN2 Regulate Prolactin-Induced STAT5 Transcription Factor Recruitment and Function in Breast Cancer Cells.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Histone H1 and Chromosomal Protein HMGN2 Regulate Prolactin-Induced STAT5 Transcription Factor Recruitment and Function in Breast Cancer Cells./
Author:	Schauwecker, Suzanne Marie.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2017,
Description:	170 p.
Notes:	Source: Dissertation Abstracts International, Volume: 78-10(E), Section: B.
Contained By:	Dissertation Abstracts International78-10B(E).
Subject:	Biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10261940
ISBN:	9781369817799

Histone H1 and Chromosomal Protein HMGN2 Regulate Prolactin-Induced STAT5 Transcription Factor Recruitment and Function in Breast Cancer Cells.
Schauwecker, Suzanne Marie.

Histone H1 and Chromosomal Protein HMGN2 Regulate Prolactin-Induced STAT5 Transcription Factor Recruitment and Function in Breast Cancer Cells. - Ann Arbor : ProQuest Dissertations & Theses, 2017 - 170 p.

Source: Dissertation Abstracts International, Volume: 78-10(E), Section: B.

Thesis (Ph.D.)--Northwestern University, 2017.

The hormone prolactin (PRL) contributes to breast cancer pathogenesis through various signaling pathways, one of the most notable being the JAK2/signal transducer and activator of transcription 5 (STAT5) pathway. PRL-induced activation of the transcription factor STAT5 results in the upregulation of numerous genes implicated in breast cancer pathogenesis. However, the molecular mechanisms that enable STAT5 to access the promoters of these genes are not well understood. Here, we show that PRL signaling induces chromatin decompaction at promoter DNA, corresponding with STAT5 binding. The chromatin-modifying protein high mobility group nucleosomal binding domain 2 (HMGN2) specifically promotes STAT5 accessibility at promoter DNA by facilitating the dissociation of the linker histone H1 in response to PRL. Knockdown of H1 rescues the decrease in PRL-induced transcription following HMGN2 knockdown, and it does so by allowing increased STAT5 recruitment. Moreover, H1 and STAT5 are shown to function antagonistically in regulating PRL-induced transcription as well as breast cancer cell biology. While reduced STAT5 activation results in decreased PRL-induced transcription and decreased cell proliferation, knockdown of H1 rescues both of these effects. Taken together, we elucidate a novel mechanism whereby the linker histone H1 prevents STAT5 binding at promoter DNA, and the PRL-induced dissociation of H1 mediated by HMGN2 is necessary to allow full STAT5 recruitment and promote the biological effects of PRL signaling.

ISBN: 9781369817799Subjects--Topical Terms:

522710
Biology.

Histone H1 and Chromosomal Protein HMGN2 Regulate Prolactin-Induced STAT5 Transcription Factor Recruitment and Function in Breast Cancer Cells.
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245 1 0 $a Histone H1 and Chromosomal Protein HMGN2 Regulate Prolactin-Induced STAT5 Transcription Factor Recruitment and Function in Breast Cancer Cells.
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520 $a The hormone prolactin (PRL) contributes to breast cancer pathogenesis through various signaling pathways, one of the most notable being the JAK2/signal transducer and activator of transcription 5 (STAT5) pathway. PRL-induced activation of the transcription factor STAT5 results in the upregulation of numerous genes implicated in breast cancer pathogenesis. However, the molecular mechanisms that enable STAT5 to access the promoters of these genes are not well understood. Here, we show that PRL signaling induces chromatin decompaction at promoter DNA, corresponding with STAT5 binding. The chromatin-modifying protein high mobility group nucleosomal binding domain 2 (HMGN2) specifically promotes STAT5 accessibility at promoter DNA by facilitating the dissociation of the linker histone H1 in response to PRL. Knockdown of H1 rescues the decrease in PRL-induced transcription following HMGN2 knockdown, and it does so by allowing increased STAT5 recruitment. Moreover, H1 and STAT5 are shown to function antagonistically in regulating PRL-induced transcription as well as breast cancer cell biology. While reduced STAT5 activation results in decreased PRL-induced transcription and decreased cell proliferation, knockdown of H1 rescues both of these effects. Taken together, we elucidate a novel mechanism whereby the linker histone H1 prevents STAT5 binding at promoter DNA, and the PRL-induced dissociation of H1 mediated by HMGN2 is necessary to allow full STAT5 recruitment and promote the biological effects of PRL signaling.
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