Provided herein are methods and compositions for screening of multiple nucleic acid sites, such as functional non-coding transcriptional regulatory elements in a cell. In particular, provided are methods and compositions, comprising: delivering to a cell a composition comprising: a single guide RNA (sgRNA) or a polynucleotide encoding the sgRNA comprising a sequence capable of hybridizing with a target sequence present in a non-coding transcriptional regulatory element, and an effector protein or one or more nucleotide sequences encoding the effector protein optionally comprising an effector domain, wherein the sgRNA hybridizes to the target sequence and forms a complex with the effector protein; and measuring gene expression upon binding of the complex to the target sequence.