Methods for making polynucleotide libraries, polynucleotide arrays, and cell libraries for high-throughput genomics analysis

A method for reducing the expression of a gene in a cell, comprising:

• (a) introducing a gene trap vector into a cell;
• (b) selecting for a cell wherein the gene trap vector has integrated into a gene;
• (c) introducing a knockdown reagent into the cell of step (b), wherein the knockdown reagent targets a sequence of the gene trap vector.

A method of producing a knockdown cell library, comprising:

• (a) introducing a gene trap vector into a plurality of cells;
• (b) selecting for cells wherein the gene trap vector has integrated into a gene;
• (c) introducing a knockdown reagent into the cells of step (b), wherein the knockdown reagent targets a sequence of the gene trap vector.

A method of regulating the expression of a gene comprising:

• (a) introducing a polynucleotide sequence comprising a sequence tag and the gene into a cell, wherein the gene is expressed in the cell, and
• (b) introducing a knockdown reagent that targets the sequence tag into the cell, wherein the knockdown reagent causes a reduction in the expression of the gene.

A method of regulating the expression of a gene comprising:

• (a) introducing a polynucleotide sequence comprising a sequence tag into a cell, wherein the polynucleotide sequence is inserted into a transcribed region of an endogenous gene sequence, and
• (b) introducing a knockdown regent that targets the sequence tag into the cell, wherein the knockdown reagent causes a reduction in the expression of the endogenous gene.

A cell comprising a polynucleotide sequence and a knockdown reagent that targets a sequence tag, wherein the polynucleotide sequence comprises the sequence tag and wherein the polynucleotide sequence is inserted into a transcribed region of an endogenous gene sequence.

A cell comprising a polynucleotide sequence and a knockdown reagent that targets a sequence tag, wherein the polynucleotide sequence comprises the sequence tag and a gene.

A conditional expression system comprising:

• (a) a gene trap or targeting vector comprising a sequence tag;
• and
• (b) a knockdown reagent that targets the sequence tag.