*2.1.1 Lactogenesis and the mammary gland transcriptome*

Lactogenesis is the hallmark of mammalians, and as such, this biological process conveys a tremendous impact in gene regulation with the objective to induce the mammary gland to lactate and coincides with the formation of colostrum and occurs in coordination with parturition. The strong effects of lactogenesis on the mammary gland at the cellular level have been consistently recorded through transcriptomic analysis (i.e., microarray or RNA sequencing) across several mammals including mouse [34–36], rats [37, 38], bovine [39–41], sheep [42], goat [43], human [44–46], pig [47], kangaroo [48], and seal [49]. The extreme changes in the transcriptome from pregnancy to lactation underscore the importance of such change in the transcriptome in the mammary gland to initiate and maintain milk synthesis. In the case of bovine, a closer look at such transcriptional changes due to the onset and throughout the lactation was reported previously in terms of fat [50] and protein [51] synthesis. During the lactation, the milk fat biosynthesis in the bovine mammary gland had a marked upregulation in the expression of genes associated with FA uptake from blood, intracellular transport/channeling, and key transcription factors associated with lipogenesis (i.e., PPARG and SREBF2) [50]. Then, in terms of milk protein synthesis, it was observed that cell membrane transporters, especially for AA and glucose, played an essential role along with insulin signaling through mTOR for the regulation of protein synthesis in the bovine mammary gland [51]. At a greater scale, the impact of lactogenesis in the mammary gland transcriptome has been associated with epigenetic changes that result in alterations in the DNA structure and consequently the available genetic information

**127**

productivity.

nutrigenomics in dairy cattle.

*Gene Regulation in Ruminants: A Nutritional Perspective*

transcriptome until milk synthesis declines in late lactation.

*2.1.2 Milk biosynthesis in the dairy cattle from a nutrigenomic approach*

pounds can directly or indirectly activate or repress the activity of TF.

*2.1.3 Transcription factors with nutrigenomic potential in dairy cattle*

for transcription [39]. Bionaz [39] observed chromatin changes (i.e., euchromatin or active transcribed chromatin and heterochromatin or tightly packed and transcriptionally unavailable chromatin) associated with lactogenesis, where a decrease of euchromatin status was observed as lactation begins and followed by an increase in euchromatin status as milk yield decreases during late lactation. The latter could be associated with natural response to lactation in the mammary gland to inhibit further epigenetic effects during the onset of lactation and to maintain a consistent

Nutrigenomics is a coined term to refer to the interactions between nutrients and the genome. However, the term nutrigenomics does not refer to the effect of nutrients on the sequence of DNA, but rather the nutrient-gene interactions through the intermediate action of transcription factors (TFs) in the short to medium term and epigenetic factors in the medium to long term. Bioactive compounds with potential nutrigenomic effects can be found in regular diets of dairy cattle, and such com-

Nutrigenomics is a product of the postgenome era and its impact on human, companion animals, and livestock species has gained more attention in recent years [52–55]. In dairy cattle, and overall in ruminants, the field can be considered in its infancy but, as argued by Coffey [56], holds great potential to improve health and

The TFs are fundamental to the study of nutrigenomics; they can act as intermediaries between dietary nutrients and the final alteration in gene expression. TFs that respond to nutrient effects can be activated directly or indirectly by nutrients, and upon activation, they translocate from the cytoplasm to the nucleus where they alter the transcription of specific target genes. Transcription factors can bind specific short DNA sequences (i.e., 6–12 nucleotides) called response elements located in the enhancer regions upstream of the actual gene sequence [57]. The ability of TF to modulate gene expression upon activation by nutrients confers these proteins a central stage in the field of nutrigenomics. Therefore, accurate identification and characterization of TF responding to specific nutrients and to what extent these TF can be manipulated through dietary effects should be the focus of future research in

Although between 2000 and 3000 TFs with sequence-specific DNA-binding domains in the human genome were estimated, only ~100 have been experimentally verified for their DNA-binding and regulatory functions [58]. The AnimalTFDB website had collected information for almost 1300 TF and almost 400 transcription cofactors for *Bos taurus* [59]. Rather than TF working independently, a regulatory network of TF has been suggested, which is essential to coordinate the response to

Among the known TF, the nuclear receptor superfamily of TF, with 48 members in the human genome, is the most important group of nutrient sensors [61]. From this superfamily, a short list of TFs has been identified as ligand-dependent nuclear receptors (LdNR), which can bind and be activated by macro- and micronutrients [55]. Recently, the main LdNR with a potential role in nutrigenomics with an emphasis in large [62] and small [24] ruminants has been reviewed. Among the LdNR associated with macronutrients such as fatty acids are the peroxisome proliferator-activated receptors (PPAR), liver X receptors (LXR), and hepatic

external stimuli and translate this into changes in gene expression [60].

*DOI: http://dx.doi.org/10.5772/intechopen.82193*

#### *Gene Regulation in Ruminants: A Nutritional Perspective DOI: http://dx.doi.org/10.5772/intechopen.82193*

*Gene Expression and Control*

increasing milk production efficiency.

**2.1 Gene regulation and milk biosynthesis**

*2.1.1 Lactogenesis and the mammary gland transcriptome*

the decline of the lactation.

increase, primarily due to an increase in world population and increased consumption in countries where milk has not traditionally been considered popular [33]. Until now, the demand of milk worldwide has been supplied by a large increase in milk yield per cow, which has been a product primarily from the selection and enhancement of management practices, including improved nutrition. However, because of the ever-increasing demand for milk and milk-derived products as stated above, there is a need to continue

Milk and milk products are an excellent source of macronutrients such as fat, protein, and carbohydrates, and contain a variety of bioactive molecules associated with health benefits, for instance, conjugated linolenic acid (CLA). The CLA has been associated with reductions in cancer development [25]. Because of its ability to contain bioactive molecules, milk has been considered a functional food. However, our ability to understand and yet manipulate the cow genome through nutrigenomic approaches to enrich specific bioactive molecules in milk is in its infancy. This calls for a continuous development of a wealth of knowledge around the various complex nutrient-gene interactions in dairy cows as well as development of nutritional models that can account for both traditional aspects of ruminant

During the lactation, the mammary gland is in charge of the final biosynthesis of milk using preformed elements from other organs (e.g., glucose synthesized in

(e.g., *de novo* fatty acids). The biosynthesis of milk in the mammary gland is highly regulated for several factors including nutrient supply (e.g., glucose, AA, and fatty acids) and hormones primarily related to hormonal changes during the onset and at

Lactogenesis is the hallmark of mammalians, and as such, this biological process conveys a tremendous impact in gene regulation with the objective to induce the mammary gland to lactate and coincides with the formation of colostrum and occurs in coordination with parturition. The strong effects of lactogenesis on the mammary gland at the cellular level have been consistently recorded through transcriptomic analysis (i.e., microarray or RNA sequencing) across several mammals including mouse [34–36], rats [37, 38], bovine [39–41], sheep [42], goat [43], human [44–46], pig [47], kangaroo [48], and seal [49]. The extreme changes in the transcriptome from pregnancy to lactation underscore the importance of such change in the transcriptome in the mammary gland to initiate and maintain milk synthesis. In the case of bovine, a closer look at such transcriptional changes due to the onset and throughout the lactation was reported previously in terms of fat [50] and protein [51] synthesis. During the lactation, the milk fat biosynthesis in the bovine mammary gland had a marked upregulation in the expression of genes associated with FA uptake from blood, intracellular transport/channeling, and key transcription factors associated with lipogenesis (i.e., PPARG and SREBF2) [50]. Then, in terms of milk protein synthesis, it was observed that cell membrane transporters, especially for AA and glucose, played an essential role along with insulin signaling through mTOR for the regulation of protein synthesis in the bovine mammary gland [51]. At a greater scale, the impact of lactogenesis in the mammary gland transcriptome has been associated with epigenetic changes that result in alterations in the DNA structure and consequently the available genetic information

nutrition and more novel molecular regulation of nutrient metabolism.

the liver) or compounds synthesized within the mammary epithelial cells

**126**

for transcription [39]. Bionaz [39] observed chromatin changes (i.e., euchromatin or active transcribed chromatin and heterochromatin or tightly packed and transcriptionally unavailable chromatin) associated with lactogenesis, where a decrease of euchromatin status was observed as lactation begins and followed by an increase in euchromatin status as milk yield decreases during late lactation. The latter could be associated with natural response to lactation in the mammary gland to inhibit further epigenetic effects during the onset of lactation and to maintain a consistent transcriptome until milk synthesis declines in late lactation.

## *2.1.2 Milk biosynthesis in the dairy cattle from a nutrigenomic approach*

Nutrigenomics is a coined term to refer to the interactions between nutrients and the genome. However, the term nutrigenomics does not refer to the effect of nutrients on the sequence of DNA, but rather the nutrient-gene interactions through the intermediate action of transcription factors (TFs) in the short to medium term and epigenetic factors in the medium to long term. Bioactive compounds with potential nutrigenomic effects can be found in regular diets of dairy cattle, and such compounds can directly or indirectly activate or repress the activity of TF.

Nutrigenomics is a product of the postgenome era and its impact on human, companion animals, and livestock species has gained more attention in recent years [52–55]. In dairy cattle, and overall in ruminants, the field can be considered in its infancy but, as argued by Coffey [56], holds great potential to improve health and productivity.
