Identification of unique, differentiation stage-specific patterns of expression of the bromodomain-containing genes Brd2, Brd3, Brd4, and Brdt in the mouse testis

Shang, Enyuan; Salazar, Glicella; Crowley, Thomas E.; Wang, Xiang; López, R.; Wang, Xiangyuan; Wolgemuth, Debra J.

doi:10.1016/j.modgep.2004.03.002

Cited by 100 publications

(108 citation statements)

References 28 publications

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“…As shown by Shang et al, 16 in the mouse, its expression is restricted to the germ line, specifically to pachytene and diplotene spermatocytes and early spermatids. Our findings are consistent with observations in the mouse.…”

Section: Discussionmentioning

confidence: 83%

Expression of SNURF–SNRPN upstream transcripts and epigenetic regulatory genes during human spermatogenesis

et al. 2009

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The imprinted domain in human 15q11-q13 is controlled by a bipartite imprinting centre (IC), which overlaps the 5 0 part of the paternally expressed SNURF -SNRPN gene. We have recently described two novel genes upstream of SNURF-SNRPN (PWRN1 and PWRN2), which are biallelically expressed in the testis. We have now found that PWRN1 represents an alternative 5 0 part of SNURF -SNRPN, and that its expression in the brain is imprinted. To determine when the locus is activated during spermatogenesis and which factors are involved in this process, we have mined gene-expression data of testicular biopsies from men with different types of spermatogenic failure. Whereas PWRN1-SNURF-SNRPN and PWRN2 are expressed in post-meiotic germ cells only, a hitherto undetected SNURF-SNRPN upstream transcript is expressed already at meiosis. Several epigenetic factors (eg, MBD1 and MBD2 isoforms, MBD3L1, SUVH39H2, BRDT, and EZH2) are upregulated at specific stages of spermatogenesis, suggesting that they play an important role in the epigenetic reprogramming during spermatogenesis.

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Section: Discussionmentioning

confidence: 83%

Expression of SNURF–SNRPN upstream transcripts and epigenetic regulatory genes during human spermatogenesis

et al. 2009

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“…Four BET proteins have been described in vertebrates, Brd2, Brd3, Brd4 and Brdt, which are broadly expressed with the exception of Brdt, where expression is restricted to the male germ line Rhee et al, 1998;Shang et al, 2004;Taniguchi et al, 1998). BET proteins, by means of two N-terminal bromodomains, recognize and associate with acetylated histones on chromatin (Kanno et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Pleiotrophin antagonizes Bromodomain-containing protein 2 (Brd2) during neuronal differentiation

García-Gutiérrez¹,

Juárez-Vicente²,

Wolgemuth³

et al. 2014

Journal of Cell Science

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Bromodomain-containing protein 2 (Brd2) is a BET family chromatin adaptor required for expression of cell-cycle-associated genes and therefore involved in cell cycle progression. Brd2 is expressed in proliferating neuronal progenitors, displays cell-cycle-stimulating activity and, when overexpressed, impairs neuronal differentiation. Paradoxically, Brd2 is also detected in differentiating neurons. To shed light on the role of Brd2 in the transition from cell proliferation to differentiation, we had previously looked for proteins that interacted with Brd2 upon induction of neuronal differentiation. Surprisingly, we identified the growth factor pleiotrophin (Ptn). Here, we show that Ptn antagonized the cell-cycle-stimulating activity associated with Brd2, thus enhancing induced neuronal differentiation. Moreover, Ptn knockdown reduced neuronal differentiation. We analyzed Ptnmediated antagonism of Brd2 in a cell differentiation model and in two embryonic processes associated with the neural tube: spinal cord neurogenesis and neural crest migration. Finally, we investigated the mechanisms of Ptn-mediated antagonism and determined that Ptn destabilizes the association of Brd2 with chromatin. Thus, Ptnmediated Brd2 antagonism emerges as a modulation system accounting for the balance between cell proliferation and differentiation in the vertebrate nervous system.

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“…The first bromodomain of Brdt, a testis-specific member of the BET sub-family of double-bromodomain-containing proteins, is essential for male germ cell differentiation expression of Brdt in mouse (Shang et al, 2004) and humans (Jones et al, 1997) affords the possibility of generating in vivo mutations of the mouse Brdt gene, because interfering with its expression would be predicted to not compromise embryonic development and overall viability. Furthermore, spermatogenesis, and spermiogenesis in particular, represents a unique model system in which to investigate the role of specific genes in the process of chromatin remodeling, one of the purported functions for bromodomain-containing proteins.…”

Section: Introductionmentioning

confidence: 99%

The first bromodomain of Brdt, a testis-specific member of the BET sub-family of double-bromodomain-containing proteins, is essential for male germ cell differentiation

et al. 2007

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*Brdt is a testis-specific member of the distinctive BET sub-family of bromodomain motif-containing proteins, a motif that binds acetylated lysines and is implicated in chromatin remodeling. Its expression is restricted to the germ line, specifically to pachytene and diplotene spermatocytes and early spermatids. Targeted mutagenesis was used to generate mice carrying a mutant allele of Brdt, Brdt ⌬BD1, which lacks only the first of the two bromodomains that uniquely characterize BET proteins. Homozygous Brdt ⌬BD1/⌬BD1 mice were viable but males were sterile, producing fewer and morphologically abnormal sperm. Aberrant morphogenesis was first detected in step 9 elongating spermatids, and those elongated spermatids that were formed lacked the distinctive foci of heterochromatin at the peri-nuclear envelope. Quantitative reverse transcription (RT)-PCR showed threefold increased levels of histone H1t (Hist1h1t) in Brdt ⌬BD1/⌬BD1 testes and chromatin immunoprecipitation revealed that Brdt protein, but not Brdt ⌬BD1 protein, was associated with the promoter of H1t. Intracytoplasmic sperm injection suggested that the DNA in the Brdt ⌬BD1 mutant sperm could support early embryonic development and yield functional embryonic stem cells. This is the first demonstration that deletion of just one of the two bromodomains in members of the BET sub-family of bromodomain-containing proteins has profound effects on in vivo differentiation.

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Identification of unique, differentiation stage-specific patterns of expression of the bromodomain-containing genes Brd2, Brd3, Brd4, and Brdt in the mouse testis

Cited by 100 publications

References 28 publications

Expression of SNURF–SNRPN upstream transcripts and epigenetic regulatory genes during human spermatogenesis

Expression of SNURF–SNRPN upstream transcripts and epigenetic regulatory genes during human spermatogenesis

Pleiotrophin antagonizes Bromodomain-containing protein 2 (Brd2) during neuronal differentiation

The first bromodomain of Brdt, a testis-specific member of the BET sub-family of double-bromodomain-containing proteins, is essential for male germ cell differentiation

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