PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis

Kim, Chang Rok; Noda, Taichi; Kim, Hyunkyung; Kim, Gibeom; Park, Seongwan; Na, Yongwoo; Oura, Seiya; Shimada, Keisuke; Bang, Injin; Ahn, Jun Yeong; Kim, Yong Ryoul; Oh, Se Kyu; Choi, Hee Jung; Kim, Jong Seo; Jung, Inkyung; Lee, Ho; Okada, Yuki; Ikawa, Masahito; Baek, Sung Hee

doi:https://doi.org/10.1016/j.celrep.2020.107950

PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis

Kim, Chang Rok; Noda, Taichi; Kim, Hyunkyung et al.

Cell Reports, 2020, 32(4), 107950

Number of Access:1,175（2025-08-22 01:06 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/78544

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Title	PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis
Creator	CreatorName Kim, Chang Rok
	NRID 1000050712551 1000050712551 CreatorName Noda, Taichi
	CreatorName Kim, Hyunkyung
	CreatorName Kim, Gibeom
	CreatorName Park, Seongwan
	CreatorName Na, Yongwoo
	CreatorName Oura, Seiya
	NRID 1000060779601 1000060779601 ORCID 0000-0003-3739-7163 0000-0003-3739-7163 researchmap permalink nununununu nununununu Scopus Author ID 56479808000 56479808000 CreatorName Shimada, Keisuke
	CreatorName Bang, Injin
	CreatorName Ahn, Jun Yeong
	CreatorName Kim, Yong Ryoul
	CreatorName Oh, Se Kyu
	CreatorName Choi, Hee Jung
	CreatorName Kim, Jong Seo
	CreatorName Jung, Inkyung
	CreatorName Lee, Ho
	NRID 1000060546430 1000060546430 CreatorName Okada, Yuki
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 CreatorName Ikawa, Masahito
	CreatorName Baek, Sung Hee
Subject	BRDT
	H3K14ub
	H4 hyperacetylation
	histone removal
	histone-to-protamine exchange
	PHF7
	spermiogenesis
Description	Chang Rok Kim, Taichi Noda, Hyunkyung Kim, Gibeom Kim, Seongwan Park, Yongwoo Na, Seiya Oura, Keisuke Shimada, Injin Bang, Jun-Yeong Ahn, Yong Ryoul Kim, Se Kyu Oh, Hee-Jung Choi, Jong-Seo Kim, Inkyung Jung, Ho Lee, Yuki Okada, Masahito Ikawa, Sung Hee Baek, PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis, Cell Reports, Volume 32, Issue 4, 2020, 107950, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2020.107950.
Abstract	Spermatogenesis is a complex process of sperm generation, including mitosis, meiosis, and spermiogenesis. During spermiogenesis, histones in post-meiotic spermatids are removed from chromatin and replaced by protamines. Although histone-to-protamine exchange is important for sperm nuclear condensation, the underlying regulatory mechanism is still poorly understood. Here, we identify PHD finger protein 7 (PHF7) as an E3 ubiquitin ligase for histone H3K14 in post-meiotic spermatids. Generation of Phf7-deficient mice and Phf7 C160A knockin mice with impaired E3 ubiquitin ligase activity reveals defects in histone-to-protamine exchange caused by dysregulation of histone removal factor Bromodomain, testis-specific (BRDT) in early condensing spermatids. Surprisingly, E3 ubiquitin ligase activity of PHF7 on histone ubiquitination leads to stabilization of BRDT by attenuating ubiquitination of BRDT. Collectively, our findings identify PHF7 as a critical factor for sperm chromatin condensation and contribute to mechanistic understanding of fundamental phenomenon of histone-to-protamine exchange and potential for drug development for the male reproduction system. Histone-to-protamine exchange is essential for functional sperm. Kim et al. demonstrate that PHF7 is an E3 ubiquitin ligase for histone H3, and that PHF7-mediated histone ubiquitination regulates BRDT stability during histone removal. Mice with impaired Phf7 show dysfunctional sperm caused by defects in histone ubiquitination and histone-to-protamine exchange.
Publisher	Elsevier B.V.
Source Title	Cell Reports
Volume (Issue)	32(4)
Page	107950
Date of Issued	2020-07-28
Language	English
Handle URL	https://hdl.handle.net/11094/78544
eISSN	22111247
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.celrep.2020.107950
Relation.isIdenticalTo	PMID 32726616
Access Rights	open access
CopyRight	© 2020 The Author(s). This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Cell Reports. 2020, 32(4), p. 107950
DC.title	PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis
DC.creator	Kim, Chang Rok
	Noda, Taichi
	Kim, Hyunkyung
	Kim, Gibeom
	Park, Seongwan
	Na, Yongwoo
	Oura, Seiya
	Shimada, Keisuke
	Bang, Injin
	Ahn, Jun Yeong
	Kim, Yong Ryoul
	Oh, Se Kyu
	Choi, Hee Jung
	Kim, Jong Seo
	Jung, Inkyung
	Lee, Ho
	Okada, Yuki
	Ikawa, Masahito
	Baek, Sung Hee
DC.publisher	Elsevier B.V.
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2020-07-28
DC.identifier	https://doi.org/10.1016/j.celrep.2020.107950
DC.subject	BRDT
	H3K14ub
	H4 hyperacetylation
	histone removal
	histone-to-protamine exchange
	PHF7
	spermiogenesis
DC.description	Chang Rok Kim, Taichi Noda, Hyunkyung Kim, Gibeom Kim, Seongwan Park, Yongwoo Na, Seiya Oura, Keisuke Shimada, Injin Bang, Jun-Yeong Ahn, Yong Ryoul Kim, Se Kyu Oh, Hee-Jung Choi, Jong-Seo Kim, Inkyung Jung, Ho Lee, Yuki Okada, Masahito Ikawa, Sung Hee Baek, PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis, Cell Reports, Volume 32, Issue 4, 2020, 107950, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2020.107950.
DCTERMS.abstract	Spermatogenesis is a complex process of sperm generation, including mitosis, meiosis, and spermiogenesis. During spermiogenesis, histones in post-meiotic spermatids are removed from chromatin and replaced by protamines. Although histone-to-protamine exchange is important for sperm nuclear condensation, the underlying regulatory mechanism is still poorly understood. Here, we identify PHD finger protein 7 (PHF7) as an E3 ubiquitin ligase for histone H3K14 in post-meiotic spermatids. Generation of Phf7-deficient mice and Phf7 C160A knockin mice with impaired E3 ubiquitin ligase activity reveals defects in histone-to-protamine exchange caused by dysregulation of histone removal factor Bromodomain, testis-specific (BRDT) in early condensing spermatids. Surprisingly, E3 ubiquitin ligase activity of PHF7 on histone ubiquitination leads to stabilization of BRDT by attenuating ubiquitination of BRDT. Collectively, our findings identify PHF7 as a critical factor for sperm chromatin condensation and contribute to mechanistic understanding of fundamental phenomenon of histone-to-protamine exchange and potential for drug development for the male reproduction system. Histone-to-protamine exchange is essential for functional sperm. Kim et al. demonstrate that PHF7 is an E3 ubiquitin ligase for histone H3, and that PHF7-mediated histone ubiquitination regulates BRDT stability during histone removal. Mice with impaired Phf7 show dysfunctional sperm caused by defects in histone ubiquitination and histone-to-protamine exchange.
DC.rights	© 2020 The Author(s). This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	78544
citation_title	PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis
citation_author	Kim, Chang Rok
	Noda, Taichi
	Kim, Hyunkyung
	Kim, Gibeom
	Park, Seongwan
	Na, Yongwoo
	Oura, Seiya
	Shimada, Keisuke
	Bang, Injin
	Ahn, Jun Yeong
	Kim, Yong Ryoul
	Oh, Se Kyu
	Choi, Hee Jung
	Kim, Jong Seo
	Jung, Inkyung
	Lee, Ho
	Okada, Yuki
	Ikawa, Masahito
	Baek, Sung Hee
citation_publisher	Elsevier B.V.
citation_language	English
citation_date	2020-07-28
citation_journal_title	Cell Reports
citation_volume	32
citation_issue	4
citation_firstpage	107950
citation_doi	https://doi.org/10.1016/j.celrep.2020.107950
citation_pmid	32726616
citation_public_url	https://hdl.handle.net/11094/78544

PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis

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