NCBI Summary:
This gene encodes a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
General function
Nucleic acid binding, DNA binding, Transcription factor
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Ovulation
Comment
Lazzaro MA, et al
report the cloning of two cDNAs, Snf2h and Snf2l, encoding the murine members of the Imitation Switch (ISWI) family of chromatin remodeling proteins. To gain insight into their function we examined the spatial and temporal expression patterns of Snf2h and Snf2l during development. In the brain, Snf2h is prevalent in proliferating cell populations whereas, Snf2l is predominantly expressed in terminally differentiated neurons after birth and in adult animals, concomitant with the expression of a neural specific isoform. Moreover, a similar proliferation/differentiation relationship of expression for these two genes was observed in the ovaries and testes of adult mice. These results are consistent with a role of Snf2h complexes in replication-associated nucleosome assembly and suggest that Snf2l complexes have distinct functions associated with cell maturation or differentiation.
Expression regulated by
LH
Comment
The ISWI protein SNF2L regulates steroidogenic acute regulatory protein (StAR) expression during terminal differentiation of ovarian granulosa cells. Lazzaro MA et al. Luteinization is a complex process, stimulated by gonadotropins, that promotes ovulation and development of the corpus luteum (CL) through terminal differentiation of granulosa cells. The pronounced expression of the mammalian ISWI genes, SNF2H and SNF2L in adult ovaries prompted us to investigate the role of these chromatin remodeling proteins during follicular development and luteinization. SNF2H expression is highest during growth of preovulatory follicles and becomes less prevalent during luteinization. In contrast, both SNF2L transcript and SNF2L protein levels are rapidly increased in granulosa cells of the mouse ovary 8 h after human chorionic gonadotropin (hCG) treatment, and continue to be expressed 36 h later within the functional CL. We demonstrate a physical interaction between SNF2L and the progesterone receptor (PR)-A isoform, which regulates PR-responsive genes required for ovulation. Moreover, chromatin immunoprecipitation demonstrated that, following gonadotropin stimulation, SNF2L is associated with the proximal promoter of the steroidogenic acute regulatory protein (StAR) gene, a classic marker of luteinization in granulosa cells. Interaction of SNF2L with the StAR promoter is required for StAR expression, as siRNA knockdown of SNF2L prevents the activation of the StAR gene. Our results provide the first indication that ISWI chromatin remodeling proteins are responsive to the LH (LH) surge and that this response is required for the activation of the StAR gene and the overall development of a functional luteal cell.
Ovarian localization
Oocyte, Cumulus, Granulosa, Luteal cells
Comment
Genomewide discovery and classification of candidate ovarian fertility genes in the mouse. Gallardo TD et al. Female infertility syndromes are among the most prevalent chronic health disorders in women, but their genetic basis remains unknown because of uncertainty regarding the number and identity of ovarian factors controlling the assembly, preservation, and maturation of ovarian follicles. To systematically discover ovarian fertility genes en masse, we employed a mouse model (Foxo3) in which follicles are assembled normally but then undergo synchronous activation. We developed a microarray-based approach for the systematic discovery of tissue-specific genes and, by applying it to Foxo3 ovaries and other samples, defined a surprisingly large set of ovarian factors (n = 348, approximately 1% of the mouse genome). This set included the vast majority of known ovarian factors, 44% of which when mutated produce female sterility phenotypes, but most were novel. Comparative profiling of other tissues, including microdissected oocytes and somatic cells, revealed distinct gene classes and provided new insights into oogenesis and ovarian function, demonstrating the utility of our approach for tissue-specific gene discovery. This study will thus facilitate comprehensive analyses of follicle development, ovarian function, and female infertility. This is an oocyte and cumulus-specific gene.
Follicle stages
Preovulatory, Corpus luteum
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: subfertile Comment: The ISWI ATPase Snf2l Is Required for Superovulation and Regulates Fgl2 in Differentiating Mouse Granulosa Cells. Ppin D et al. Imitation Switch (ISWI) proteins are catalytic subunits of chromatin remodeling complexes that alter nucleosome positioning by hydrolyzing ATP to regulate access to DNA. In mice there are two paralogs, SNF2-homolog (SNF2H) and SNF2-like (SNF2L), which participate in different complexes and have contrasting patterns of expression. Here we investigate the role of SNF2L in ovaries by characterizing a mouse bearing an inactivating deletion of exon 6 which disrupts the ATPase domain. Snf2l mutant mice produce significantly fewer eggs than control mice when superovulated. Gonadotropin stimulation leads to a significant deficit in secondary follicles and an increase in abnormal antral follicles. Mutant females also fail to induce Fibrinogen-like 2 (Fgl2) in response to human chorionic gonadotropin (hCG), while overexpression of SNF2L is sufficient to drive its expression in granulosa cells. SNF2L is also shown to directly interact with the nuclear receptor co-activator Flightless I (FLI-I) as shown by immunoprecipitation. These results begin to establish a role for SNF2L in the precise coordination of gene expression in granulosa cells during folliculogenesis, and its broader implications in fertility.