Mouse BRWD1 is critical for spermatid postmeiotic transcription and female meiotic chromosome stability

Pattabiraman, S. R.; Baumann, Claudia; Guisado, Daniela; Eppig, John J.; Schimenti, John C.; Fuente, Rabindranath De La

doi:10.1083/jcb.201404109

Cited by 42 publications

(35 citation statements)

References 73 publications

(123 reference statements)

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“…However, we (data not shown) and others [18] detected BRD4 solely in spermatogonia. Recently, it has been shown that the dual bromodomain-containing protein BRWD1 is involved in transcription of about 300 genes, most of which are activated in spermatids [59].…”

Section: Discussionmentioning

confidence: 99%

Murine and Human Spermatids Are Characterized by Numerous, Newly Synthesized and Differentially Expressed Transcription Factors and Bromodomain-Containing Proteins

Klaus

Gonzalez

Bergmann

et al. 2016

Biology of Reproduction

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Much of spermatid differentiation takes place in the absence of active transcription, but in the early phase, large amounts of mRNA are synthesized, translationally repressed, and stored. Most nucleosomal histones are then degraded, and chromatin is repackaged by protamines. For both transcription and the histone-to-protamine transition in differentiating spermatids, chromatin must be opened. This raises the question of whether two different processes exist. It is conceivable that for initiation of the histone-to-protamine transition, the already accessible, actively transcribed chromatin regions are utilized or vice versa. We analyzed the enrichment of different canonical TATA-boxbinding, protein-associated factors and their variants in murine spermatids, diverse bromodomain-containing proteins, and components of the Polycomb repressive complexes PRC1 and PRC2 using quantitative PCR. We compared the enrichment of corresponding proteins in human and murine spermatids and analyzed the time frame of postmeiotic transcription and expression of histones, transition proteins, and protamines in human and murine spermatids using immunohistology. We correlated the expression of different transcription factors and bromodomain-containing proteins and the pattern of acetylated histones to active transcription and to the histone-to-protamine transition in both human and murine spermatids. Our findings suggest that differentiating spermatids use both common and specific features to open chromatin first for transcription and subsequently for histone-to-protamine transition.

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Section: Discussionmentioning

confidence: 99%

Murine and Human Spermatids Are Characterized by Numerous, Newly Synthesized and Differentially Expressed Transcription Factors and Bromodomain-Containing Proteins

Klaus

Gonzalez

Bergmann

et al. 2016

Biology of Reproduction

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“…Modified histones are recognized by 'reader' proteins, which are often components of chromatin-remodeling complexes that are involved in the histone-to-protamine transition. For example, bromodomain-containing proteins, such as BRDT and BRWD1, bind to hyperacetylated histones before histone removal from the chromatin, and mice lacking BRWD1 or expressing mutant BRDT are sterile due to impaired spermiogenesis (Pattabiraman et al, 2015;Shang et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Little is known about the factors that drive expression of the TSSK genes during spermatogenesis, with the exception of TSSK6 (also known as small serine/threonine kinase, SSTK), which is highly dependent on BRWD1 (Pattabiraman et al, 2015). Heat shock protein 90 (HSP90) is essential for the stability of all TSSKs and for catalytic activation of TSSK2 and TSSK4 (Jha et al, 2013(Jha et al, , 2010.…”

Section: Introductionmentioning

confidence: 99%

TSSK6 is required for γH2AX formation and the histone-to-protamine transition during spermiogenesis

Jha

Tripurani

Johnson

2017

Journal of Cell Science

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Spermiogenesis includes transcriptional silencing, chromatin condensation and extensive morphological changes as spermatids transform into sperm. Chromatin condensation involves histone hyperacetylation, transitory DNA breaks, histone H2AX (also known as H2AFX) phosphorylation at Ser139 (γH2AX), and replacement of histones by protamines. Previously, we have reported that the spermatid protein kinase TSSK6 is essential for fertility in mice, but its specific role in spermiogenesis is unknown. Here, we show that TSSK6 expression is spatiotemporally coincident with γH2AX formation in the nuclei of developing mouse spermatids. RNAsequencing analysis demonstrates that genetic ablation of Tssk6 does not impact gene expression or silencing in spermatids. However, loss of TSSK6 blocks γH2AX formation, even though the timing and level of the transient DNA breaks is unaltered. Further, Tssk6-knockout sperm contained increased levels of histones H3 and H4, and protamine 2 precursor and intermediate(s) indicative of a defective histone-to-protamine transition. These results demonstrate that TSSK6 is required for γH2AX formation during spermiogenesis, and also link γH2AX to the histone-to-protamine transition and male fertility.

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“…Spermiogenesis is a complex postmeiotic process during which gross morphological, biochemical, and physiological modifications of round spermatids create the mature spermatozoa (Steger, ). During spermiogenesis, the round spermatids elongate, acquire an acrosomal cap, develop a tail, and extrude most of their cytoplasm as residual bodies; while their nuclei undergo extensive condensation as the histones are replaced by protamines (Pattabiraman et al, ). These protamines tightly pack the spermatid DNA for stringent, temporal regulation of stage‐specific gene expression, which is required for the differentiation of round spermatids into mature sperm (Steger, ).…”

Section: Introductionmentioning

confidence: 99%

The dynamics of gene expression during and post meiosis sets the sperm agenda

Pandey

Yadav

Vishvkarma

et al. 2019

Molecular Reproduction Devel

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Meiosis is the defining event of spermatogenesis. Spermatocytes undergo meiosis to give rise to round spermatids, which in turn metamorphose to flagellated spermatozoa that mature in the epididymis. To characterize the dynamics of gene expression during these important stages of spermatogenesis, we undertook transcriptome analysis in >90% pure pachytene spermatocytes and round spermatids, and pure mature sperm of rat by massive parallel deep sequencing. The study has identified 10,719 total transcripts expressed in meiotic and postmeiotic cells, out of which 7,641 were present in all the three cell types. Most abundant transcripts were related to gametogenesis in spermatocytes and spermatids, and mitochondrial energy metabolism in sperm. Importantly, 108 transcripts were specific to spermatocytes, including Cpeb2, Dpf3, H2afy, Haus7, Plcb1, Taf9, and Tdrd7 strongly linked with meiosis. Similarly, 323 transcripts unique to round spermatids included Arpc5, Apoa1, Cntrob, Dcaf17, Ift88, and Ly6k that play essential roles in spermiogenesis. Likewise, 178 transcripts unique to sperm included Camta1, Hoxb1, and Prdx6 having assigned roles in fertility and/or embryonic development. Levels of ~16% transcripts declined from spermatocytes to sperm while two (Cd300e and Ddx17) increased. New candidate genes with possible roles in meiosis (91), spermiogenesis (298), and sperm function (171), have been identified. This study has provided new potential targets for contraception and/or treatment of male infertility. (CDRI communication number 9889).

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Mouse BRWD1 is critical for spermatid postmeiotic transcription and female meiotic chromosome stability

Abstract: Exhibiting sexually dimorphic roles in mice, BRWD1 is essential for proper meiotic chromosome condensation and telomere structure during oogenesis and for haploid-specific gene transcription during postmeiotic sperm differentiation.

Cited by 42 publications

References 73 publications

Murine and Human Spermatids Are Characterized by Numerous, Newly Synthesized and Differentially Expressed Transcription Factors and Bromodomain-Containing Proteins

Murine and Human Spermatids Are Characterized by Numerous, Newly Synthesized and Differentially Expressed Transcription Factors and Bromodomain-Containing Proteins

TSSK6 is required for γH2AX formation and the histone-to-protamine transition during spermiogenesis

The dynamics of gene expression during and post meiosis sets the sperm agenda

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