HP1BP3 expression determines maternal behavior and offspring survival

B. P. Garfinkel; S. Arad; S. M. Neuner; S. Netser; S. Wagner; C. C. Kaczorowski; C. J. Rosen; M. Gal; H. Soreq; J. Orly

doi:10.1111/gbb.12312

HP1BP3 expression determines maternal behavior and offspring survival

B. P. Garfinkel, S. Arad, S. M. Neuner, S. Netser, S. Wagner, C. C. Kaczorowski, C. J. Rosen, M. Gal, H. Soreq, J. Orly

Department of Neurobiology

Research output: Contribution to journal › Article › peer-review

Abstract

Maternal care is an indispensable behavioral component necessary for survival and reproductive success in mammals, and postpartum maternal behavior is mediated by an incompletely understood complex interplay of signals including effects of epigenetic regulation. We approached this issue using our recently established mice with targeted deletion of heterochromatin protein 1 binding protein 3 (HP1BP3), which we found to be a novel epigenetic repressor with critical roles in postnatal growth. Here, we report a dramatic reduction in the survival of pups born to Hp1bp3^−/− deficient mouse dams, which could be rescued by co-fostering with wild-type dams. Hp1bp3^−/− females failed to retrieve both their own pups and foster pups in a pup retrieval test, and showed reduced anxiety-like behavior in the open-field and elevated-plus-maze tests. In contrast, Hp1bp3^−/− females showed no deficits in behaviors often associated with impaired maternal care, including social behavior, depression, motor coordination and olfactory capability; and maintained unchanged anxiety-associated hallmarks such as cholinergic status and brain miRNA profiles. Collectively, our results suggest a novel role for HP1BP3 in regulating maternal and anxiety-related behavior in mice and call for exploring ways to manipulate this epigenetic process.

Original language	English
Pages (from-to)	678-688
Number of pages	11
Journal	Genes, Brain and Behavior
Volume	15
Issue number	7
DOIs	https://doi.org/10.1111/gbb.12312
State	Published - 1 Sep 2016

Bibliographical note

Funding Information:
The authors wish to thank Professors Adi Mizrahi and Raz Yirmiya and Dr Yael Shlomai-Fuchs for their most helpful advice and discussions regarding maternal and social behavior. Ilan Friedson, Uriya Bekenstein and Dr Nibha Mishra, Jerusalem for help with preparation and analysis of deep sequencing. The sequencing was performed at the Center for Genomic Technologies at the Hebrew University of Jerusalem. This work was supported by The United States – Israel Binational Science Foundation (grant number 2013194 to JO and CJR), and by the European Research Council (Advanced Award 321501, to HS). BPG is supported by a fellowship from the Edmond and Lilly Safra Center for Brain Sciences. SA is a scholarship recipient of the Joint Research Fund of The Hebrew University Faculty of Medicine, Hadassah-Shaare Zedek-Kaplan Medical Centers. The authors have no conflicts of interest to declare.

Publisher Copyright:
© 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society

Keywords

Anxiety
HP1BP3
chromatin
epigenetics
histone
knockout mouse
maternal behavior
microRNA
social
survival

ASJC Scopus subject areas

Genetics
Neurology
Behavioral Neuroscience

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10.1111/gbb.12312

Cite this

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title = "HP1BP3 expression determines maternal behavior and offspring survival",

abstract = "Maternal care is an indispensable behavioral component necessary for survival and reproductive success in mammals, and postpartum maternal behavior is mediated by an incompletely understood complex interplay of signals including effects of epigenetic regulation. We approached this issue using our recently established mice with targeted deletion of heterochromatin protein 1 binding protein 3 (HP1BP3), which we found to be a novel epigenetic repressor with critical roles in postnatal growth. Here, we report a dramatic reduction in the survival of pups born to Hp1bp3−/− deficient mouse dams, which could be rescued by co-fostering with wild-type dams. Hp1bp3−/− females failed to retrieve both their own pups and foster pups in a pup retrieval test, and showed reduced anxiety-like behavior in the open-field and elevated-plus-maze tests. In contrast, Hp1bp3−/− females showed no deficits in behaviors often associated with impaired maternal care, including social behavior, depression, motor coordination and olfactory capability; and maintained unchanged anxiety-associated hallmarks such as cholinergic status and brain miRNA profiles. Collectively, our results suggest a novel role for HP1BP3 in regulating maternal and anxiety-related behavior in mice and call for exploring ways to manipulate this epigenetic process.",

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note = "Funding Information: The authors wish to thank Professors Adi Mizrahi and Raz Yirmiya and Dr Yael Shlomai-Fuchs for their most helpful advice and discussions regarding maternal and social behavior. Ilan Friedson, Uriya Bekenstein and Dr Nibha Mishra, Jerusalem for help with preparation and analysis of deep sequencing. The sequencing was performed at the Center for Genomic Technologies at the Hebrew University of Jerusalem. This work was supported by The United States – Israel Binational Science Foundation (grant number 2013194 to JO and CJR), and by the European Research Council (Advanced Award 321501, to HS). BPG is supported by a fellowship from the Edmond and Lilly Safra Center for Brain Sciences. SA is a scholarship recipient of the Joint Research Fund of The Hebrew University Faculty of Medicine, Hadassah-Shaare Zedek-Kaplan Medical Centers. The authors have no conflicts of interest to declare. Publisher Copyright: {\textcopyright} 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society",

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doi = "10.1111/gbb.12312",

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AU - Neuner, S. M.

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AU - Wagner, S.

AU - Kaczorowski, C. C.

AU - Rosen, C. J.

AU - Gal, M.

AU - Soreq, H.

AU - Orly, J.

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AB - Maternal care is an indispensable behavioral component necessary for survival and reproductive success in mammals, and postpartum maternal behavior is mediated by an incompletely understood complex interplay of signals including effects of epigenetic regulation. We approached this issue using our recently established mice with targeted deletion of heterochromatin protein 1 binding protein 3 (HP1BP3), which we found to be a novel epigenetic repressor with critical roles in postnatal growth. Here, we report a dramatic reduction in the survival of pups born to Hp1bp3−/− deficient mouse dams, which could be rescued by co-fostering with wild-type dams. Hp1bp3−/− females failed to retrieve both their own pups and foster pups in a pup retrieval test, and showed reduced anxiety-like behavior in the open-field and elevated-plus-maze tests. In contrast, Hp1bp3−/− females showed no deficits in behaviors often associated with impaired maternal care, including social behavior, depression, motor coordination and olfactory capability; and maintained unchanged anxiety-associated hallmarks such as cholinergic status and brain miRNA profiles. Collectively, our results suggest a novel role for HP1BP3 in regulating maternal and anxiety-related behavior in mice and call for exploring ways to manipulate this epigenetic process.

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KW - HP1BP3

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KW - epigenetics

KW - histone

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KW - maternal behavior

KW - microRNA

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KW - survival

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JO - Genes, Brain and Behavior

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ER -

HP1BP3 expression determines maternal behavior and offspring survival

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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