NCBI Summary:
The protein encoded by this gene is 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. The protein encoded by this gene is a component of the chromatin remodeling and spacing factor RSF, a facilitator of the transcription of class II genes by RNA polymerase II. The encoded protein is similar in sequence to the Drosophila ISWI chromatin remodeling protein. [provided by RefSeq, Jul 2008]
General function
Chromosome organization, DNA Replication
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Germ cell development, Oocyte maturation, Early embryo development
Comment
The chromatin remodeler Snf2h is essential for oocyte meiotic cell cycle progression. Zhang C et al. (2020) Oocytes are indispensable for mammalian life. Thus, it is important to understand how mature oocytes are generated. As a critical stage of oocytes development, meiosis has been extensively studied, yet how chromatin remodeling contributes to this process is largely unknown. Here, we demonstrate that the ATP-dependent chromatin remodeling factor Snf2h (also known as Smarca5) plays a critical role in regulating meiotic cell cycle progression. Females with oocyte-specific depletion of Snf2h are infertile and oocytes lacking Snf2h fail to undergo meiotic resumption. Mechanistically, depletion of Snf2h results in dysregulation of meiosis-related genes, which causes failure of maturation-promoting factor (MPF) activation. ATAC-seq analysis in oocytes revealed that Snf2h regulates transcription of key meiotic genes, such as Prkar2b, by increasing its promoter chromatin accessibility. Thus, our studies not only demonstrate the importance of Snf2h in oocyte meiotic resumption, but also reveal the mechanism underlying how a chromatin remodeling factor can regulate oocyte meiosis.//////////////////
A gene expression signature shared by human mature oocytes and embryonic stem cells. Assou S et al. ABSTRACT: BACKGROUND: The first week of human pre-embryo development is characterized by the induction of totipotency and then pluripotency. The understanding of this delicate process will have far reaching implication for in vitro fertilization and regenerative medicine. Human mature MII oocytes and embryonic stem (ES) cells are both able to achieve the feat of cell reprogramming towards pluripotency, either by somatic cell nuclear transfer or by cell fusion, respectively. Comparison of the transcriptome of these two cell types may highlight genes that are involved in pluripotency initiation. Results: Based on a microarray compendium of 205 samples, we compared the gene expression profile of mature MII oocytes and human ES cells (hESC) to that of somatic tissues. We identified a common oocyte/hESC gene expression profile, which included a strong cell cycle signature, genes associated with pluripotency such as LIN28 and TDGF1, a large chromatin remodelling network (TOP2A, DNMT3B, JARID2, SMARCA5, CBX1, CBX5), 18 different zinc finger transcription factors, including ZNF84, and several still poorly annotated genes such as KLHL7, MRS2, or the Selenophosphate synthetase 1 (SEPHS1). Interestingly, a large set of genes was also found to code for proteins involved in the ubiquitination and proteasome pathway. Upon hESC differentiation into embryoid bodies, the transcription of this pathway declined. In vitro, we observed a selective sensitivity of hESC to the inhibition of the activity of the proteasome. Conclusions: These results shed light on the gene networks that are concurrently overexpressed by the two human cell types with somatic cell reprogramming properties.
Expression regulated by
Comment
Ovarian localization
Oocyte, Granulosa
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.
Follicle stages
Preovulatory
Comment
Zheng P, et al reported the expression of genes encoding chromatin regulatory factors in developing rhesus monkey oocytes and preimplantation stage embryos: possible roles in genome activation.
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.
Phenotypes
Mutations
1 mutations
Species: D. melanogaster
Mutation name: None
type: naturally occurring fertility: infertile - ovarian defect Comment: Stem cell self-renewal controlled by chromatin remodeling factors.
Xi R, et al .
The self-renewing ability of a stem cell is controlled by its specialized micro-environment or niche, whereas epigenetic regulation of gene expression by chromatin remodeling factors underlies cell fate determination. Here we report that the adenosine triphosphate-dependent chromatin remodeling factors ISWI and DOM control germline stem cell and somatic stem cell self-renewal in the Drosophila ovary, respectively. The iswi mutant germline stem cells are lost rapidly because of defects in responding to bone morphogenetic protein niche signals and in repressing differentiation, whereas the dom mutant somatic stem cells are lost because of defective self-renewal. This work demonstrates that different stem cell types can use different chromatin remodeling factors to control cell self-renewal.