The let-7 miRNA was one of the first miRNAs discovered in the nematode, Caenorhabditis elegans, and its biological functions show a high level of evolutionary conservation from the nematode to the human. Unlike in C. elegans, higher animals have multiple isoforms of let-7 miRNAs; these isoforms share a consensus sequence called the ‘seed sequence’ and these isoforms are categorized into let-7 miRNA family. The expression of let-7 family is required for developmental timing and tumor suppressor function, but must be suppressed for the self-renewal of stem cells. Therefore, let-7 miRNA biogenesis must be carefully controlled. To generate a let-7 miRNA, a primary transcript is produced by RNA polymerase II and then subsequently processed by Drosha/DGCR8, TUTase, and Dicer. Because dysregulation of let-7 processing is deleterious, biogenesis of let-7 is tightly regulated by cellular factors, such as the RNA binding proteins, LIN28A/B and DIS3L2. In this review, we discuss the biological functions and biogenesis of let-7 miRNAs, focusing on the molecular mechanisms of regulation of let-7 biogenesis in vertebrates, such as the mouse and the human.

Chromatin remodeling is emerging as a central mechanism for patterning and differentiation in multicellular eukaryotes. SWI/SNF chromatin remodeling ATPases are conserved in the animal and plant kingdom and regulate transcriptional programs in response to endogenous and exogenous cues. In contrast with their metazoan orthologs, null mutants in two Arabidopsis thaliana SWI/SNF ATPases, BRAHMA (BRM) and SPLAYED (SYD), are viable, facilitating investigation of their role in the organism. Previous analyses revealed that syd and brm null mutants exhibit both similar and distinct developmental defects, yet the functional relationship between the two closely related ATPases is not understood. Another central question is whether these proteins act as general or specific transcriptional regulators. Using global expression studies, double mutant analysis, and protein interaction assays, we find overlapping functions for the two SWI/SNF ATPases. This partial diversification may have allowed expansion of the SWI/SNF ATPase regulatory repertoire, while preserving essential ancestral functions. Moreover, only a small fraction of all genes depends on SYD or BRM for expression, indicating that these SWI/SNF ATPases exhibit remarkable regulatory specificity. Our studies provide a conceptual framework for understanding the role of SWI/SNF chromatin remodeling in regulation of Arabidopsis development.

The timing of the switch from vegetative to reproductive development is crucial for species survival. The plant-specific transcription factor and meristem identity regulator LEAFY (LFY) controls this switch in Arabidopsis, in part via the direct activation of two other meristem identity genes, APETALA1 (AP1) and CAULIFLOWER (CAL). We recently identified five new direct LFY targets as candidates for the missing meristem identity regulators that act downstream of LFY. Here, we demonstrate that one of these, the class I homeodomain leucine-zipper transcription factor LMI1, is a meristem identity regulator. LMI1 acts together with LFY to activate CAL expression. The interaction between LFY, LMI1 and CAL resembles a feed-forward loop transcriptional network motif. LMI1 has additional LFY-independent roles in the formation of simple serrated leaves and in the suppression of bract formation. The temporal and spatial expression of LMI1 supports a role in meristem identity and leaf/bract morphogenesis.

SNF2 chromatin-remodeling ATPases play an important role in ensuring proper development in higher eukaryotes by controlling accessibility of cis-regulatory DNA regions to transcription factors and to the transcriptional machinery. However, the biological targets controlled by these ATPases are largely unknown. Using genetic and molecular analyses we have identified WUSCHEL (WUS) as a biologically important target of the SNF2-class ATPase SPLAYED (SYD) in the shoot apical meristem of Arabidopsis. We present evidence that SYD is recruited to the WUS promoter and that it is involved in regulation of the stem cell pool maintenance via direct transcriptional control of this master regulator. Supplemental material is available at http://www.genesdev.org.